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Li Y, Pan AP, Yu AY. Recent Progression of Pathogenesis and Treatment for Diabetic Cataracts. Semin Ophthalmol 2024:1-8. [PMID: 39530428 DOI: 10.1080/08820538.2024.2427789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 10/22/2024] [Accepted: 10/31/2024] [Indexed: 11/16/2024]
Abstract
Background: Cataracts are still the main cause of blindness worldwide. The incidence of cataracts in the diabetic population is 3-5 times higher than in healthy people. With the increasing incidence of diabetes and the development of aging, as well as the higher risk of surgical and postoperative complications of diabetic patients undergoing surgery, it is still necessary to study the occurrence and development mechanism of diabetic cataracts as well as potential therapeutic targets and therapeutic drugs.Methods: A retrospective review of the literature from PubMed (2017-2024).Results: We summarized the the current literature on the molecular mechanism and prevention and treatment of diabetic cataracts.Conclusions: The aqueous humor metabolism changes, oxidative stress, reactive oxygen species generation increase, the conversion of polyol pathway, as well as non-coding RNA expression changes play important roles in diabetic cataract and these processes is closely linked with each other. Inhibitors or drugs target to these processes, such as aldose reductase inhibitors, antioxidants, natural flavonoid compounds, as well as nanotechnology-based therapeutic product, have shown promising prospects in the prevention and treatment of diabetic cataract.
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Affiliation(s)
- Yike Li
- Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang P. R. China
- National Clinical Research Center for Ocular Diseases, Wenzhou, Zhejiang, P. R. China
| | - An-Peng Pan
- Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang P. R. China
- National Clinical Research Center for Ocular Diseases, Wenzhou, Zhejiang, P. R. China
| | - A-Yong Yu
- Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang P. R. China
- National Clinical Research Center for Ocular Diseases, Wenzhou, Zhejiang, P. R. China
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Chen X, Li Y, Lu L, Wu J, Yan R, Xiang J, Fan Q, Liu J, Li S, Xue Y, Fu T, Liu J, Li Z. Activation of the SST-SSTR5 signaling pathway enhances corneal wound healing in diabetic mice. Mucosal Immunol 2024; 17:858-870. [PMID: 38866206 DOI: 10.1016/j.mucimm.2024.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 04/23/2024] [Accepted: 06/04/2024] [Indexed: 06/14/2024]
Abstract
Corneal wound healing in diabetic patients is usually delayed and accompanied by excessive inflammation. However, the underlying cellular and molecular mechanisms remain poorly understood. Here, we found that somatostatin (SST), an immunosuppressive peptide produced by corneal nerve fibers, was significantly reduced in streptozotocin-induced diabetic mice. In addition, we discovered that topical administration of exogenous SST significantly improved re-epithelialization and nerve regeneration following diabetic corneal epithelial abrasion. Further analysis showed that topical SST significantly reduced the expression of injury inflammation-related genes, inhibited neutrophil infiltration, and shifted macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 in diabetic corneas' healing. Moreover, the application of L-817,818, an agonist of the SST receptor type 5 subtype, significantly reduced the inflammatory response following epithelial injury and markedly improved the process of re-epithelialization and nerve regeneration in mice. Taken together, these data suggest that activation of the SST-SST receptor type 5 pathway significantly ameliorates diabetes-induced abnormalities in corneal wound repair in mice. Targeting this pathway may provide a novel strategy to restore impaired corneal wound closure and nerve regeneration in diabetic patients.
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Affiliation(s)
- Xinwei Chen
- International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, School of Medicine, Jinan University, Guangzhou, China
| | - Yan Li
- International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, School of Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Liyuan Lu
- International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, School of Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Jiaxin Wu
- International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, School of Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Ruyu Yan
- International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, School of Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Jiayan Xiang
- International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, School of Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Qiwei Fan
- International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, School of Medicine, Jinan University, Guangzhou, China
| | - Jiangman Liu
- International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, School of Medicine, Jinan University, Guangzhou, China
| | - Senmao Li
- International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, School of Medicine, Jinan University, Guangzhou, China
| | - Yunxia Xue
- International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, School of Medicine, Jinan University, Guangzhou, China
| | - Ting Fu
- International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, School of Medicine, Jinan University, Guangzhou, China
| | - Jun Liu
- International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, School of Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China; Guangdong-Hong Kong-Macau Great Bay Area Geroscience Joint Laboratory, School of Medicine, Jinan University, Guangzhou, China.
| | - Zhijie Li
- International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, School of Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
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Fathi-Karkan S, Amiri Ramsheh N, Arkaban H, Narooie-Noori F, Sargazi S, Mirinejad S, Roostaee M, Sargazi S, Barani M, Malahat Shadman S, Althomali RH, Rahman MM. Nanosuspensions in ophthalmology: Overcoming challenges and enhancing drug delivery for eye diseases. Int J Pharm 2024; 658:124226. [PMID: 38744414 DOI: 10.1016/j.ijpharm.2024.124226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2024] [Revised: 04/30/2024] [Accepted: 05/11/2024] [Indexed: 05/16/2024]
Abstract
This review article provides a comprehensive overview of the advancements in using nanosuspensions for controlled drug delivery in ophthalmology. It highlights the significance of ophthalmic drug delivery due to the prevalence of eye diseases and delves into various aspects of this field. The article explores molecular mechanisms, drugs used, and physiological factors affecting drug absorption. It also addresses challenges in treating both anterior and posterior eye segments and investigates the role of mucus in obstructing micro- and nanosuspensions. Nanosuspensions are presented as a promising approach to enhance drug solubility and absorption, covering formulation, stability, properties, and functionalization. The review discusses the pros and cons of using nanosuspensions for ocular drug delivery and covers their structure, preparation, characterization, and applications. Several graphical representations illustrate their role in treating various eye conditions. Specific drug categories like anti-inflammatory drugs, antihistamines, glucocorticoids, and more are discussed in detail, with relevant studies. The article also addresses current challenges and future directions, emphasizing the need for improved nanosuspension stability and exploring potential technologies. Nanosuspensions have shown substantial potential in advancing ophthalmic drug delivery by enhancing solubility and absorption. This article is a valuable resource for researchers, clinicians, and pharmaceutical professionals in this field, offering insights into recent developments, challenges, and future prospects in nanosuspension use for ocular drug delivery.
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Affiliation(s)
- Sonia Fathi-Karkan
- Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd 94531-55166, Iran; Department of Advanced Sciences and Technologies in Medicine, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd 9414974877, Iran.
| | - Nasim Amiri Ramsheh
- Catalysts and Organic Synthesis Research Laboratory, Department of Chemistry, Iran University of Science and Technology, 16846, Tehran, Iran.
| | - Hasan Arkaban
- Department of Chemistry, University of Isfahan, Isfahan 8174673441, Iran.
| | - Foroozan Narooie-Noori
- Optometry Department, School of Rehabilitation, Tehran University of Medical Sciences, Tehran, Iran.
| | - Sara Sargazi
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran.
| | - Shekoufeh Mirinejad
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran.
| | - Maryam Roostaee
- Department of Chemistry, Faculty of Sciences, Vali-e-Asr University of Rafsanjan, Rafsanjan, Iran.
| | - Saman Sargazi
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran; Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
| | - Mahmood Barani
- Department of Chemistry, Faculty of Nano and Bio Science and Technology, Persian Gulf University, Bushehr 75168, Iran.
| | | | - Raed H Althomali
- Department of Chemistry, College of Art and Science, Prince Sattam bin Abdulaziz University, Wadi Al-Dawasir 11991, Al Kharj, Saudi Arabia.
| | - Mohammed M Rahman
- Center of Excellence for Advanced Materials Research (CEAMR) & Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
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Alhalwani AY, Jambi S, Borai A, Khan MA, Almarzouki H, Elsayid M, Aseri AF, Taher NO, Alghamdi A, Alshehri A. Assessment of the systemic immune-inflammation index in type 2 diabetic patients with and without dry eye disease: A case-control study. Health Sci Rep 2024; 7:e1954. [PMID: 38698793 PMCID: PMC11063262 DOI: 10.1002/hsr2.1954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Revised: 02/12/2024] [Accepted: 02/19/2024] [Indexed: 05/05/2024] Open
Abstract
Background The inflammation plays a role in the pathophysiology of type-2 diabetes progression, and the mechanism remains unclear. The systemic immune-inflammation index (SII) is a novel inflammatory marker for type 2 diabetes patients and integrates multiple indicators in complete blood counts and routine blood tests. Aim Since there is no international diagnostic standard for dry eye disease (DED), this study uses low-cost inflammatory blood biomarkers to investigate the correlation between SII and DM2-DED and determine the diagnosis indices of other biomarkers in DM2-DED. Methodology A case-control retrospective analysis of totel patients n = 293 randomly selected and categorized into four groups: DED, DM2, DM2-DED, and healthy subjects. Demographic and blood biomarker variables were classified as categorical and continuous variables. The platelet-to-lymphocyte ratio (PLR), lymphocytes-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio (NLR), and SII were calculated platelet count multiply by NLR and analyzed for their correlation for all groups. Results Focusing on DM2-DED patients was more common in females, 59.6%, than in males, 40.2%. The mean ages were 60.7 ± 11.85 years, a statistically significant difference with all groups. In the study group DM2-DED, there was an increase in all blood markers compared to all remaining groups except PLR. Only neutrophil, hemoglobin A1c (HbA1c), and fasting blood sugar levels were statistically significant differences in DM2-DED patients (p > 0.001, p < 0.001, and p < 0.001, respectively) compared to all groups. There was a positive correlation between HbA1c and PLR, HbA1c and NLR, and HbA1c and SII (r = 0.037, p = 0.705; r = 0.031, p = 0.754; and r = 0.066, p < 0.501, respectively) in the DM2-DED group. Conclusion This study demonstrated that elevated SII values were linked to elevated HbA1c in DM2-DED patients. The potential of SII and HbA1c as early diagnostic indicators for ocular problems associated with diabetes mellitus is highlighted by their favorable connection in diagnosing DM2-DED.
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Affiliation(s)
- Amani Y. Alhalwani
- College of Science and Health ProfessionsKing Saud bin Abdulaziz University for Health SciencesJeddahSaudi Arabia
- Department of Biomedical ResearchKing Abdullah International Medical Research CenterJeddahSaudi Arabia
| | - Shatha Jambi
- College of Science and Health ProfessionsKing Saud bin Abdulaziz University for Health SciencesJeddahSaudi Arabia
- Department of Biomedical ResearchKing Abdullah International Medical Research CenterJeddahSaudi Arabia
| | - Anwar Borai
- College of Science and Health ProfessionsKing Saud bin Abdulaziz University for Health SciencesJeddahSaudi Arabia
- Department of Biomedical ResearchKing Abdullah International Medical Research CenterJeddahSaudi Arabia
- King Abdulaziz Medical CityJeddahSaudi Arabia
| | - Muhammad Anwar Khan
- College of Science and Health ProfessionsKing Saud bin Abdulaziz University for Health SciencesJeddahSaudi Arabia
- Department of Biomedical ResearchKing Abdullah International Medical Research CenterJeddahSaudi Arabia
| | - Hashem Almarzouki
- College of Science and Health ProfessionsKing Saud bin Abdulaziz University for Health SciencesJeddahSaudi Arabia
- Department of Biomedical ResearchKing Abdullah International Medical Research CenterJeddahSaudi Arabia
- King Abdulaziz Medical CityJeddahSaudi Arabia
| | - Mohieldin Elsayid
- College of Science and Health ProfessionsKing Saud bin Abdulaziz University for Health SciencesJeddahSaudi Arabia
- Department of Biomedical ResearchKing Abdullah International Medical Research CenterJeddahSaudi Arabia
| | | | - Nada O. Taher
- College of Science and Health ProfessionsKing Saud bin Abdulaziz University for Health SciencesJeddahSaudi Arabia
| | - Ali Alghamdi
- Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia
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Yang ZM, Huang X, Liu SH, Deng LS, Wang X. Sustained release gel based on CT image inspection for treatment of diabetes fundus macular lesions. Med Eng Phys 2024; 126:104148. [PMID: 38621848 DOI: 10.1016/j.medengphy.2024.104148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 02/23/2024] [Accepted: 03/09/2024] [Indexed: 04/17/2024]
Abstract
Currently, slow-release gel therapy is considered to be an effective treatment for fundus macular disease, but the lack of effective evaluation methods limits its clinical application. Therefore, the purpose of this study was to investigate the application and clinical effect of slow-release gel based on CT image examination in the treatment of diabetic fundus macular disease. CT images of fundus macular lesions were collected in a group of diabetic patients. Then the professional image processing software is used to process and analyze the image and extract the key parameters. A slow-release gel was designed and prepared, and applied to the treatment of diabetic fundus macular disease. CT images before and after treatment were compared and analyzed, and the effect of slow-release gel was evaluated. In a certain period of time after treatment, the lesion size and lesion degree of diabetic fundus macular disease were significantly improved by using slow-release gel therapy with CT image examination. No significant adverse reactions or complications were observed during the treatment. This indicates that the slow-release gel based on CT image examination is a safe, effective and feasible treatment method for diabetic fundus macular disease. This method can help improve the vision and quality of life of patients, and provide a new idea and plan for clinical treatment.
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Affiliation(s)
- Zhu-Min Yang
- Department of Ophthalmology, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China
| | - Xing Huang
- Department of Ophthalmology, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China
| | - Sheng-Hui Liu
- Department of Ophthalmology, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China
| | - Li-Shi Deng
- Department of Ophthalmology, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China
| | - Xian Wang
- Department of Ophthalmology, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China.
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Zajner C, Moayad L, Popovic MM, Kertes PJ, Kohly RP, Wong D, Muni RH. Relationship Between Disease and Treatment Factors in Diabetes With Vision Difficulty: A Cross-Sectional, Population-Based Analysis. Ophthalmic Surg Lasers Imaging Retina 2024; 55:142-153. [PMID: 38270564 DOI: 10.3928/23258160-20240110-01] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2024]
Abstract
BACKGROUND AND OBJECTIVE Relationships between disease and treatment factors of diabetes and vision difficulty remain largely unknown. This study investigated the relationship between disease and treatment factors in diabetes and participants' self-reported vision difficulty. PATIENTS AND METHODS This was a cross-sectional, population-based analysis. Data from the National Health Interview Survey was used and analyzed through univariable and multivariable logistic regression. RESULTS From the 29,464 included participants, logistic regression showed increased odds of self-reported vision difficulty among participants with diabetes (odds ratio [OR] = 2.14, P < 0.001), prediabetes (OR = 1.95, P < 0.001), or gestational diabetes (OR = 1.54, P < 0.001) compared to participants without diabetes. Those who reported having diabetes for more than a year had higher odds of vision difficulty (OR = 1.97, P = 0.02), as did those who were taking insulin (OR = 1.62, P < 0.001), those who had taken less insulin to save money within the past year (OR = 1.87, P = 0.01), and those who reported experiencing diabetes-related stress (OR = 2.14, P < 0.001). CONCLUSIONS Duration of diabetes, diabetes-related stress, and taking less insulin than recommended to save money were associated with vision difficulty. [Ophthalmic Surg Lasers Imaging Retina 2024;55:142-153.].
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Khan J, Shaw S. Risk of cataract and glaucoma among older persons with diabetes in India: a cross-sectional study based on LASI, Wave-1. Sci Rep 2023; 13:11973. [PMID: 37488196 PMCID: PMC10366202 DOI: 10.1038/s41598-023-38229-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Accepted: 07/05/2023] [Indexed: 07/26/2023] Open
Abstract
According to the International Diabetes Federation-2019 estimates, India is home to 77 million diabetic individuals which is projected to grow up to 147.2 million by 2045. Diabetes being a progressive health disorder leads to multiple morbidities and complications including eye diseases and visual impairments. As the burden of diabetes mellitus is increasing, eye problems like cataracts and glaucoma are commonly cited problems among the older adults. In this context, this study aims to provide the public health evidences on diabetes associated burden and risk of developing cataracts and glaucoma among older adults aged 60 and above in India. The analytical sample of this cross-sectional study comprised of 31,464 individuals aged 60 and above. Bivariate cross-tabulation and chi-square test were performed to understand the differential in the prevalence of cataracts and glaucoma by diabetes mellitus including the socio-economic and demographic characteristics of the individuals. Binary logistic regression estimation was executed to estimate the adjusted odds ratio for each of the outcome variables within a multivariate framework. The cataract problem affects more than one-fifth of the older people, while glaucoma affects 2% of them. The prevalence of cataract and glaucoma is 29% among diabetic older adults compared to 22% among non-diabetic persons. In terms of gender, the cataract prevalence is comparatively higher among females (25%) than males (21%). It is important to note that while adjusting for socio-economic and demographic characteristics, the likelihood of cataract (AOR 1.495; p-value < 0.01) and glaucoma (AOR 1.554; p-value < 0.01) is significantly higher among older adults with diabetes than among their counterparts. Medical practitioners should conduct prognosis for diabetic eye problems among patients and raise awareness about the potential risks of developing vision loss, such as cataracts and glaucoma, which are more prevalent among individuals with diabetes.
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Affiliation(s)
- Junaid Khan
- Department of Population and Development, International Institute for Population Sciences, Mumbai, India
| | - Subhojit Shaw
- Department of Population and Development, International Institute for Population Sciences, Mumbai, India.
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Emade N, Nyamori J, Njuguna M, Njambi L, Gichuhi S. Vision-Related Quality of Life among Patients Attending the Diabetes and Eye Clinics in Kenyatta National Hospital, Kenya. J Ophthalmol 2023; 2023:7809692. [PMID: 36703703 PMCID: PMC9873415 DOI: 10.1155/2023/7809692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 12/19/2022] [Accepted: 12/30/2022] [Indexed: 01/19/2023] Open
Abstract
Objective Our main objective was to determine the overall vision-related quality of life (VRQoL) among patients with diabetes mellitus attending the diabetes and eye clinics in Kenyatta National Hospital, Kenya. Design Analytical cross-sectional study conducted in December 2020 setting: This study was performed at the Diabetes and Eye Clinics in Kenyatta National Hospital, the main national referral centre in Nairobi, Kenya. Participants. Using a purposive consecutive sampling method, we enrolled 100 participants, 50 with diabetic retinopathy and 50 without diabetic retinopathy. Main Outcomes and Measures. We compared the VRQoL of participants with diabetic retinopathy with those without diabetic retinopathy and assessed whether VRQoL worsened with increasing the severity of diabetic retinopathy. VRQoL was assessed using the World Health Organization/Prevention of Blindness and Deafness Vision Function-20 Questionnaire (VF-20). With this tool, the higher the mean score, the worse the quality of life. Diabetic retinopathy was graded using the Early Treatment of Diabetic Retinopathy Study. VRQoL trend with DR were analysed using the worse eye. Results Participants with diabetic retinopathy had worse overall total VRQoL mean score (33.4, SD11.5) than those without (26.9, SD 4.7) in all domains; overall self-rating, 2.6 vs. 2.2, p < 0.001; general functioning, 18.0 vs. 14.7, p=0.005; psychosocial, 6.7 vs. 5.3, p < 0.001; and visual symptoms, 6.1 vs. 4.8, p < 0.001. VRQoL was worse with increasing severity of diabetic retinopathy in all domains moving from mild NPDR to moderate NPDR, severe NPDR and PDR, overall self-rating (2.2, 2.5, 3.5, 3.3; p < 0.001); visual symptoms (5.6, 5.6, 7.5, 7.4; p=0.002); psychosocial (5.7, 6.5, 6.0 8.8; p=0.004); and general functioning (15.7, 16.9, 17.5 23.6; p=0.014). Presence of DR, distance vision impairment, and diabetic macula oedema were associated with low overall self-rating. Conclusion and Relevance. Our findings underscore the need for interventions for early detection and management of diabetic retinopathy to prevent developing more advanced DR and its associated deterioration of VRQoL.
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Affiliation(s)
- Nerice Emade
- MMed Ophthal, University of Nairobi, Nairobi, Kenya
| | - Joseph Nyamori
- Department of Ophthalmology, University of Nairobi, Nairobi, Kenya
| | - Margaret Njuguna
- Department of Ophthalmology, University of Nairobi, Nairobi, Kenya
| | - Lucy Njambi
- Department of Ophthalmology, University of Nairobi, Nairobi, Kenya
| | - Stephen Gichuhi
- Head Department of Ophthalmology, University of Nairobi, Nairobi, Kenya
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Yalcın SO, Kaplan AT, Sobu E. Corneal endothelial cell morphology and optical coherence tomography findings in children with type 1 diabetes mellitus. Eur J Ophthalmol 2022; 33:1331-1339. [PMID: 36544297 DOI: 10.1177/11206721221145983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Purpose To evaluate central macular thickness, retinal nerve fibre layer thickness, corneal endothelial cell density and central corneal thickness in children with Type 1 Diabetes Mellitus (DM). Methods Thirty children with Type 1 DM and 30 age-matched children as controls were examined. Central macular thickness (CMT) and four quadrants of retinal nerve fibre layer thickness (RNFLT) were measured by optical coherence tomography (OCT), while endothelial cell density (ECD), coefficient of variation in cell size (CV), hexagonality (HEX) and central corneal thickness (CCT) were measured by noncontact specular microscopy. Results The mean ECD was 2810.77 ± 273.47 cells/mm2 and the mean hexagonality ratio was 49.77 ± 13.2 both were significantly lower (p < 0.001, p = 0.037 respectively) in the diabetic group compared to the control group. The mean CV was 37.6 ± 7.27, it was significantly higher (p = 0.024) in the diabetic group than the control group. The mean corneal thickness was greater in the DM group than the controls, but the difference was not significant (p = 0.176). There were no significant differences in CMT or RNFLT between the two groups. There was a negative correlation between the HbA1c levels and the thickness of the superior quadrants of RNFL (r = -0.406, p = 0.026). The duration of diabetes had no significant correlations with the corneal and retinal parameters. Conclusion The diabetic children had changes in corneal endothelial morphology and there was a negative correlation between HbA1c levels and superior quadrant of RNFLT.
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Affiliation(s)
- Sibel Oskan Yalcın
- Department of Ophthalmology, Kartal Dr. Lütfi Kırdar City Hospital, İstanbul, Turkey
| | - Aysin Tuba Kaplan
- Department of Ophthalmology, Kartal Dr. Lütfi Kırdar City Hospital, İstanbul, Turkey
| | - Elif Sobu
- Department of Pediatric Endocrinology, Kartal Dr. Lütfi Kırdar City Hospital, İstanbul, Turkey
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Xia Y. The management of cataract surgery in diabetic patients. J Perioper Pract 2022; 32:361-367. [PMID: 35445624 DOI: 10.1177/17504589221091063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
A cataract in the eye is a major cause of vision loss in diabetic patients, which occurs earlier and develops faster than non-diabetic patients, and often requires surgery for treatment. However, diabetic patients undergoing cataract surgery have a higher risk of intraoperative and postoperative complications than non-diabetic patients. For diabetic patients undergoing any surgery, careful perioperative assessment and management are required to reduce postoperative complications and improve surgical outcomes. Better understanding of their needs may guide perioperative practitioners to manage their care appropriately. This article presents recent evidence and guidance associated with the preoperative, intraoperative and postoperative management of diabetic patients undergoing cataract surgery and to inform perioperative practitioners of the challenges and potential complications to provide the best care and improve sight.
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Affiliation(s)
- Yu Xia
- Beijing Aerospace General Hospital, Beijing, China
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11
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Solomon SD, Shoge RY, Ervin AM, Contreras M, Harewood J, Aguwa UT, Olivier MMG. Improving Access to Eye Care: A Systematic Review of the Literature. Ophthalmology 2022; 129:e114-e126. [PMID: 36058739 DOI: 10.1016/j.ophtha.2022.07.012] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 07/12/2022] [Accepted: 07/14/2022] [Indexed: 01/02/2023] Open
Abstract
PURPOSE The goals were to develop a working and inclusive definition of access to eye care, identify gaps in the current system that preclude access, and highlight recommendations that have been identified in prior studies. This manuscript serves as a narrative summary of the literature. CLINICAL RELEVANCE Health care disparities continue to plague the nation's well-being, and eye care is no exception. Inequities in eye care negatively affect disease processes (i.e., glaucoma, cataracts, diabetic retinopathy), interventions (surgical treatment, prescription of glasses, referrals), and populations (gender, race and ethnicity, geography, age). METHODS A systematic review of the existing literature included all study designs, editorials, and opinion pieces and initially yielded nearly 2500 reports. To be included in full-text review, an article had to be US-based, be written in English, and address 1 or more of the key terms "barriers and facilitators to health care," "access," and "disparities in general and sub-specialty eye care." Both patient and health care professional perspectives were included. One hundred ninety-six reports met the inclusion criteria. RESULTS Four key themes regarding access to eye care from both patient and eye care professional perspectives emerged in the literature: (1) barriers and facilitators to access, (2) utilization, (3) compliance and adherence, and (4) recommendations to improve access. Common barriers and facilitators included many factors identified as social determinants of health (i.e., transportation, insurance, language, education). Utilization of eye care was largely attributable to having coverage for eye care, recommendations from primary care professionals, and improved health status. Geographic proximity, age, and lack of transportation surfaced as factors for compliance and adherence. There were a variety of recommendations to improve access to eye care, including improving presence in community health clinics, reimbursement for physicians, and funding of community-based programs such as DRIVE and REACH. CONCLUSIONS The eye care profession has abundant evidence of the disparities that continue to affect marginalized communities. Improving community-based programs and clinics, addressing social determinants of health, and acknowledging the effects of discrimination and bias on eye care serve as ways to improve equity in this field.
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Affiliation(s)
- Sharon D Solomon
- School of Medicine, Johns Hopkins University, Baltimore, Maryland.
| | - Ruth Y Shoge
- School of Optometry, University of California Berkeley, Berkeley, California
| | - Ann Margret Ervin
- School of Medicine, Johns Hopkins University, Baltimore, Maryland; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland
| | - Melissa Contreras
- College of Optometry, Marshall B. Ketchum University, Fullerton, California
| | | | - Ugochi T Aguwa
- School of Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Mildred M G Olivier
- Chicago Medical School, Rosalind Franklin University of Medicine and Science, Chicago, Illinois
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12
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Koliaki C, Katsilambros N. Repositioning the Role of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) on the TRAIL to the Development of Diabetes Mellitus: An Update of Experimental and Clinical Evidence. Int J Mol Sci 2022; 23:ijms23063225. [PMID: 35328646 PMCID: PMC8949963 DOI: 10.3390/ijms23063225] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 03/14/2022] [Accepted: 03/15/2022] [Indexed: 01/25/2023] Open
Abstract
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF protein superfamily, represents a multifaceted cytokine with unique biological features including both proapoptotic and pro-survival effects in different cell types depending on receptor interactions and local stimuli. Beyond its extensively studied anti-tumor and immunomodulatory properties, a growing body of experimental and clinical evidence over the past two decades suggests a protective role of TRAIL in the development of type 1 (T1DM) and type 2 (T2DM) diabetes mellitus. This evidence can be briefly summarized by the following observations: (i) acceleration and exacerbation of T1DM and T2DM by TRAIL blockade or genetic deficiency in animal models, (ii) prevention and amelioration of T1DM and T2DM with recombinant TRAIL treatment or systemic TRAIL gene delivery in animal models, (iii) significantly reduced circulating soluble TRAIL levels in patients with T1DM and T2DM both at disease onset and in more advanced stages of diabetes-related complications such as cardiovascular disease and diabetic nephropathy, (iv) increase of serum TRAIL levels in diabetic patients after initiation of antidiabetic treatment and metabolic improvement. To explore the underlying mechanisms and provide mechanistic links between TRAIL and diabetes, a number of animal and in vitro studies have reported direct effects of TRAIL on several tissues involved in diabetes pathophysiology such as pancreatic islets, skeletal muscle, adipose tissue, liver, kidney, and immune and vascular cells. Residual controversy remains regarding the effects of TRAIL on adipose tissue homeostasis. Although the existing evidence is encouraging and paves the way for investigating TRAIL-related interventions in diabetic patients with cardiometabolic abnormalities, caution is warranted in the extrapolation of animal and in vitro data to the clinical setting, and further research in humans is imperative in order to uncover all aspects of the TRAIL-diabetes relationship and delineate its therapeutic implications in metabolic disease.
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13
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The Corneal Changes in Diabetic Patients. SERBIAN JOURNAL OF EXPERIMENTAL AND CLINICAL RESEARCH 2021. [DOI: 10.2478/sjecr-2020-0045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Abstract
Diabetes mellitus (DM) represents a systemic disorder which afects different organs. Ocular complications of the DM are the worldwide leading cause of blindness. The most common complications are diabetic retinopathy, diabetic cataract, neovascular glaucoma. Recently many investigations point out that DM can cause comlications at ocular surface as well. Condition such as decreased corneal sensitivity, dry eye or neurotrophic corneal ulceraction are the main clinical manifestations of the diabetic keratopathy (DK). Untreated, these conditions can lead to serious visual acuity decrease. Pathological processes, based on chronic inflammation, due to chronic hyperglycemia, are the main step in the process of DK development. Adequate treatment of the main disease - DM is an imperative in maintaining the healthy cornea without subjective sensations of diabetic patients.
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14
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Mohsen F, Safieh H, Shibani M, Ismail H, Alzabibi MA, Armashi H, Sawaf B. Assessing diabetes mellitus knowledge among Syrian medical students: A cross-sectional study. Heliyon 2021; 7:e08079. [PMID: 34632146 PMCID: PMC8488477 DOI: 10.1016/j.heliyon.2021.e08079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 07/13/2021] [Accepted: 09/24/2021] [Indexed: 11/30/2022] Open
Abstract
Background Diabetes mellitus is the fastest growing global health emergency of the 21st century. The Middle East and North Africa region have the highest prevalence of diabetes in the world. Since medical students are the pillars of future healthcare systems, their knowledge of the disease must be evaluated, updated, and enhanced appropriately. Methods A cross-sectional study was conducted at the Syrian Private University (SPU) in November 2019 on World Diabetes Day in Damascus, during the Syrian war crisis. Data were collected through self-administered questionnaires and analyzed using the Statistical Package for Social Sciences version 25.0 (SPSS Inc., United States). Results Of the 275 students, 74 (26.9%) were preclinical students and 201 (73%) were clinical students with a mean age of 21.9 (±3.70) years. 67 (25.0%) are overweight, and 26 (9.7%) are obese. Students revealed a good level of knowledge regarding clinical features, risk factors, and complications; however, a lack of knowledge was noticed in the general information and the diagnostic criteria section. Clinical year students (4th, 5th, 6th) demonstrated higher levels of awareness compared to students in pre-clinical years (1st, 2nd, 3rd). Conclusions Knowledge and awareness of medical students about diabetes mellitus were found to have some gaps. Health education efforts are required to reinforce its identification and management at all levels, while also encouraging lifestyle modifications among our students.
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Affiliation(s)
- Fatema Mohsen
- Faculty of Medicine, Syrian Private University, Damascus, Syria
| | - Homam Safieh
- Faculty of Medicine, Syrian Private University, Damascus, Syria
| | - Mosa Shibani
- Faculty of Medicine, Syrian Private University, Damascus, Syria
| | - Hlma Ismail
- Faculty of Medicine, Syrian Private University, Damascus, Syria
| | | | - Humam Armashi
- Faculty of Medicine, Syrian Private University, Damascus, Syria
| | - Bisher Sawaf
- Internal Medicine Department, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.,Department of Internal Medicine, Faculty of Medicine, Syrian Private University, Damascus, Syria
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15
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Fan F, Li X, Li K, Jia Z. To Find Out the Relationship Between Levels of Glycosylated Hemoglobin with Meibomian Gland Dysfunction in Patients with Type 2 Diabetes. Ther Clin Risk Manag 2021; 17:797-807. [PMID: 34393486 PMCID: PMC8355550 DOI: 10.2147/tcrm.s324423] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 07/21/2021] [Indexed: 12/14/2022] Open
Abstract
Aim The aim of this study was to investigate the relationship between levels of glycosylated hemoglobin (HbA1c) with meibomian gland dysfunction (MGD) in patients with type 2 diabetes mellitus (T2DM) and to further explore the related influencing factors. Methods Totally, 167 patients with T2DM and 68 non-diabetic subjects were selected. Further, T2DM patients were divided into 2 groups based on 7% HbA1c. Standard patient evaluation of eye dryness (SPEED), lipid layer thickness (LLT), partial blink (PB) ratio, percentage of partial glands (MGP), meibomian gland yielding liquid secretion (MGYLS), meibomian gland yielding secretion score (MGYSS), line of marx (LOM), tear break up time (TBUT), tear meniscus height (TMH) and Schirmer I test (SIT) were applied to evaluate meibomian gland function. Finally, the correlation between HbA1c and various indicators was also analyzed. Results Between HbA1c≥7% group and HbA1c<7% group, the differences in LLT (P=0.003), MGP (P<0.001), MGYLS (P=0.014) and TBUT (P=0.015) were all statistically significant. Compared with the non-diabetic group, LLT (P=0.020), MBP (P<0.001), MGYS (P< 0.001), TBUT (P<0.001), SIT (P=0.001), TMH (P=0.017) and LOM (P<0.001) were significantly different in HbA1c≥7% group, while the differences of MBP (P=0.031), MGYSS (P<0.001), SIT (P=0.001) and LOM (P<0.001) in HbA1c≤7% group were statistically significant. Besides, the prevalence of MGD in HbA1c≥7% group was evidently higher than that in non-diabetic group (P=0.002). Correlation analysis showed that HbA1c was significantly associated with the LTT and MGP. Conclusion HbA1c≥7% is likely to result in meibomian gland function dysfunctions in T2DM patients, especially related to LLT and MGP.
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Affiliation(s)
- Fang Fan
- Department of Ophthalmology, Hebei General Hospital, Shijiazhuang, 050051, People's Republic of China
| | - Xiaodan Li
- Department of Ophthalmology, Shijiazhuang People's Hospital, Shijiazhuang, 050000, People's Republic of China
| | - Kejun Li
- Department of Ophthalmology, Hebei General Hospital, Shijiazhuang, 050051, People's Republic of China
| | - Zhiyang Jia
- Department of Ophthalmology, Hebei General Hospital, Shijiazhuang, 050051, People's Republic of China
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16
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Long P, He M, Zhang X, Luo T, Shen Y, Liu H, Jiang W, Han F, Hu Y. Protective effect of aldehyde dehydrogenase 2 against rat corneal dysfunction caused by streptozotocin-induced type I diabetes. Exp Biol Med (Maywood) 2021; 246:1740-1749. [PMID: 33969723 PMCID: PMC8719039 DOI: 10.1177/15353702211013308] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Accepted: 04/09/2021] [Indexed: 11/15/2022] Open
Abstract
Aldehyde dehydrogenase 2 plays a pivotal role in detoxifying aldehydes, and our previous study revealed that aldehyde dehydrogenase 2 could alleviate diabetic retinopathy-associated damage. We aimed to characterize the potential role of aldehyde dehydrogenase 2 in diabetic keratopathy. Twenty-four rats with streptozotocin-induced (60 mg/kg, single intraperitoneal injection) type 1 diabetes mellitus (T1DM) were divided the T1DM group and the T1DM + Alda1 (an activator of aldehyde dehydrogenase 2) group (5 mg/kg/d, intraperitoneal injection, 1/2/3 months), while an additional 12 healthy rats served as the control group. Corneal morphology was examined in vivo and in vitro at one, two, and three months after T1DM induction. Additionally, serum inflammatory factors were measured by ELISA, and the expression of corneal vascular endothelial growth factor A (VEGF-A) and aldehyde dehydrogenase 2 was measured by immunofluorescence staining. Corneal cell death was evaluated by terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) staining. Slit lamp analysis showed that the area of corneal epithelial cell injury in the T1DM + Alda1 group was significantly smaller than that in the T1DM group at one and two months after T1DM induction (all P < 0.05). OCT analysis and HE staining showed that the central corneal thickness (indication of corneal edema) and the epithelial keratinization level in the T1DM + Alda1 group was evidently decreased compared with those in the T1DM group (all P < 0.05). The serum inflammatory factors interleukin-1 and interleukin-6 were significantly upregulated in the T1DM group compared with the T1DM + Alda1 group at three months after T1DM induction (all P < 0.05), while there were no differences in SOD or TNF-α levels among all groups. Furthermore, corneal VEGF-A expression and corneal cell death in the T1DM + Alda1 group were dramatically reduced compared to those in the T1DM group (all P < 0.05). In conclusion, the aldehyde dehydrogenase 2 agonist Alda1 attenuated rat corneal dysfunction induced by T1DM by alleviating corneal edema, decreasing corneal cell death, and downregulating corneal VEGF-A expression.
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Affiliation(s)
- Pan Long
- Department of Ophthalmology, General Hospital of Western Theater Command, Chengdu 610083, PR China
| | - Mengshan He
- Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China
| | - Xi Zhang
- Department of Ophthalmology, General Hospital of Western Theater Command, Chengdu 610083, PR China
| | - Tao Luo
- Department of Ophthalmology, General Hospital of Western Theater Command, Chengdu 610083, PR China
| | - Yang Shen
- Department of Ophthalmology, General Hospital of Western Theater Command, Chengdu 610083, PR China
| | - Heng Liu
- Department of Ophthalmology, General Hospital of Western Theater Command, Chengdu 610083, PR China
| | - Wei Jiang
- Department of Ophthalmology, General Hospital of Western Theater Command, Chengdu 610083, PR China
| | - Fei Han
- Department of Ophthalmology, General Hospital of Western Theater Command, Chengdu 610083, PR China
| | - Yonghe Hu
- Traditional Chinese Medicine (TCM) Department, General Hospital of Western Theater Command, Chengdu 610083, PR China
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17
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Pannexin1: Role as a Sensor to Injury Is Attenuated in Pretype 2 Corneal Diabetic Epithelium. ACTA ACUST UNITED AC 2021; 2021:4793338. [PMID: 34336553 PMCID: PMC8295002 DOI: 10.1155/2021/4793338] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Accepted: 07/07/2021] [Indexed: 11/17/2022]
Abstract
Epithelial wound healing is essential to repair the corneal barrier function after injury and requires coordinated epithelial sheet movement over the wounded region. The presence and role of pannexin1 on multilayered epithelial sheet migration was examined in unwounded and wounded corneal epithelium from C57BL/6J (B6) control and diet-induced obese (DiO) mice, a pretype 2 diabetic model. We hypothesize that pannexin1 is dysregulated, and the interaction of two ion-channel proteins (P2X7 and pannexin1) is altered in pretype 2 diabetic tissue. Pannexin1 was found to be present along cell borders in unwounded tissue, and no significant difference was observed between DiO and B6 control. However, an epithelial debridement induced a striking difference in pannexin1 localization. The B6 control epithelium displayed intense staining near the leading edge, which is the region where calcium mobilization was detected, whereas the staining in the DiO corneal epithelium was diffuse and lacked distinct gradation in intensity back from the leading edge. Cells distal to the wound in the DiO tissue were irregular in shape, and the morphology was similar to that of epithelium inhibited with 10Panx, a pannexin1 inhibitor. Pannexin1 inhibition reduced mobilization of calcium between cells near the leading edge, and MATLAB scripts revealed a reduction in cell-cell communication that was also detected in cultured cells. Proximity ligation was performed to determine if P2X7 and pannexin1 interaction was a necessary component of motility and communication. While there was no significant difference in the interaction in unwounded DiO and B6 control corneal epithelium, there was significantly less interaction in the wounded DiO corneas both near the wound and back from the edge. The results demonstrate that pannexin1 contributes to the healing response, and P2X7 and pannexin1 coordination may be a required component of cell-cell communication and an underlying reason for the lack of pathologic tissue migration.
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18
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Lu X, Vick S, Chen Z, Chen J, Watsky MA. Effects of Vitamin D Receptor Knockout and Vitamin D Deficiency on Corneal Epithelial Wound Healing and Nerve Density in Diabetic Mice. Diabetes 2020; 69:1042-1051. [PMID: 32139594 PMCID: PMC7171964 DOI: 10.2337/db19-1051] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Accepted: 02/23/2020] [Indexed: 12/20/2022]
Abstract
Diabetic keratopathy occurs in ∼70% of all people with diabetes. This study was designed to examine the effects of vitamin D receptor knockout (VDR-/-) and vitamin D deficiency (VDD) on corneal epithelial wound healing and nerve density in diabetic mice. Diabetes was induced using the low-dose streptozotocin method. Corneal epithelial wounds were created using an Algerbrush, and wound healing was monitored over time. Corneal nerve density was measured in unwounded mice. VDR-/- and VDD diabetic mice (diabetic for 8 and 20 weeks, respectively) had slower healing ratios than wild-type diabetic mice. VDR-/- and VDD diabetic mice also showed significantly decreased nerve density. Reduced wound healing ratios and nerve densities were not fully rescued by a supplemental diet rich in calcium, lactose, and phosphate. We conclude that VDR-/- and VDD significantly reduce both corneal epithelial wound healing and nerve density in diabetic mice. Because the supplemental diet did not rescue wound healing or nerve density, these effects are likely not specifically related to hypocalcemia. This work supports the hypothesis that low vitamin D levels can exacerbate preexisting ophthalmic conditions, such as diabetes.
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Affiliation(s)
- Xiaowen Lu
- Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA
| | - Sarah Vick
- Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA
| | - Zhong Chen
- Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA
| | - Jie Chen
- Biostatistics and Data Science, Department of Population Health Sciences, Medical College of Georgia, Augusta University, Augusta, GA
| | - Mitchell A Watsky
- Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA
- The Graduate School, Augusta University, Augusta, GA
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19
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Zhao H, He Y, Ren YR, Chen BH. Corneal alteration and pathogenesis in diabetes mellitus. Int J Ophthalmol 2019; 12:1939-1950. [PMID: 31850180 DOI: 10.18240/ijo.2019.12.17] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Accepted: 08/12/2019] [Indexed: 12/15/2022] Open
Abstract
The incidence of diabetes mellitus (DM) and its complications have increased considerably worldwide. Diabetic keratopathy is the major complication of the cornea characterized by delayed corneal wound healing, decreasing corneal epithelial sensitivity, and recurrent corneal ulcers. There is accumulating evidence that diabetic keratopathy is correlated with the hyperglycemic state. Different corneal components may produce different alterations under hyperglycemia. In addition, diabetic nerve alteration may become a novel biomarker of early-stage DM. Abnormalities of the corneal nerve plexus have been associated with diabetic inflammatory states. There is rapidly growing evidence based on investigations of diabetic corneal nerves through in vivo confocal microscopy. Understanding the molecular pathogenesis caused by hyperglycemia may assist in the identification of novel biomarkers, as well as therapeutic targets for early treatment. This review mainly summarizes recent findings on corneal alteration and pathogenesis in DM.
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Affiliation(s)
- Han Zhao
- Department of Ophthalmology, the Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China.,Hunan Clinical Research Center of Ophthalmic Disease, Changsha 410011, Hunan Province, China
| | - Yan He
- Department of Ophthalmology, the Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China.,Hunan Clinical Research Center of Ophthalmic Disease, Changsha 410011, Hunan Province, China
| | - Yue-Rong Ren
- Department of Ophthalmology, the Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China.,Hunan Clinical Research Center of Ophthalmic Disease, Changsha 410011, Hunan Province, China
| | - Bai-Hua Chen
- Department of Ophthalmology, the Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China.,Hunan Clinical Research Center of Ophthalmic Disease, Changsha 410011, Hunan Province, China
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20
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Comparison of Corneal Parameters of Children with Diabetes Mellitus and Healthy Children. J Ophthalmol 2019; 2019:2037072. [PMID: 31781373 PMCID: PMC6875226 DOI: 10.1155/2019/2037072] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Accepted: 09/20/2019] [Indexed: 12/05/2022] Open
Abstract
Purpose To compare differences in central corneal thickness (CCT), corneal curvature, and other corneal measurements of children with diabetes mellitus (DM) and healthy children, and to investigate related factors. Methods This was a case-control study. From January to February 2018, 50 children with diabetes mellitus were selected as a case group, and 46 healthy children and adolescents without diabetes mellitus were selected as a control group. Corneal topography and CCT were analyzed using a corneal topography measuring apparatus and biometrics (IOL Master). In the diabetic group, we analyzed whether age, course of disease, sex, glycosylated hemoglobin, triglyceride level, total cholesterol, body mass index (BMI), parental BMI, birth history, feeding history, pregnancy, or puerperal history were related to corneal morphology. Results There was a significant difference in CCT between groups, but no significant differences were found in corneal diameter, corneal curvature R1 or R2, or corneal topography. Central corneal thickness was not correlated with other clinical factors in the diabetes group. Conclusion Early screening and close follow-up of keratopathy in children with diabetes are imperative.
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21
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Wang S, Jia Y, Li T, Wang A, Gao L, Yang C, Zou H. Dry Eye Disease Is More Prevalent in Children with Diabetes than in Those without Diabetes. Curr Eye Res 2019; 44:1299-1305. [PMID: 31294638 DOI: 10.1080/02713683.2019.1641827] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Purpose: To compare the prevalence of dry eye disease between children with and without diabetes, and analyze the factors associated with dry eye disease in children with diabetes.Materials and methods: 38 children with diabetes were selected as cases, and 40 children without diabetes constituted the control group. The prevalence of dry eye disease in both groups was statistically analyzed. Related factors of dry eye disease were analyzed in children with diabetes.Results: The prevalence of dry eye disease in the case group was significantly higher than that in the control group (P < .01), with the attributable proportion among the exposed (0.827) and the population attributable fraction (0.700). Univariate analysis showed that the diabetes duration, best-corrected visual acuity, corneal sensation, and levels of glycosylated hemoglobin were associated with dry eye disease in children with diabetes. Logistic regression analysis revealed that only diabetes duration and corneal sensation were independent factors associated with dry eye disease. The diabetes duration was significantly higher and the level of corneal sensation was significantly lower in subjects with dry eye disease than in those without dry eye disease.Conclusions: Early screening and close follow-up of dry eye disease in children with diabetes should be strictly implemented, especially in children with a long duration of diabetes and those with peripheral neuropathy.
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Affiliation(s)
- Shanshan Wang
- Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Fundus Diseases, Shanghai, China.,Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China.,Shanghai Eye Diseases Prevention & Treatment Center, Shanghai Eye Hospital, Shanghai, China
| | - Yan Jia
- Department of Ophthalmology, Children's Hospital of Fudan University, Shanghai, China
| | - Tao Li
- Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Fundus Diseases, Shanghai, China.,Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China.,Shanghai Eye Diseases Prevention & Treatment Center, Shanghai Eye Hospital, Shanghai, China
| | - Anken Wang
- Department of Ophthalmology, Children's Hospital of Fudan University, Shanghai, China
| | - Lu Gao
- Department of Ophthalmology, Children's Hospital of Fudan University, Shanghai, China
| | - Chenhao Yang
- Department of Ophthalmology, Children's Hospital of Fudan University, Shanghai, China
| | - Haidong Zou
- Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Fundus Diseases, Shanghai, China.,Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China.,Shanghai Eye Diseases Prevention & Treatment Center, Shanghai Eye Hospital, Shanghai, China
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22
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ČESKÁ BURDOVÁ M, KULICH M, DOTŘELOVÁ D, MAHELKOVÁ G. Effect of Diabetes Mellitus Type 1 Diagnosis on the Corneal Cell Densities and Nerve Fibers. Physiol Res 2018; 67:963-974. [DOI: 10.33549/physiolres.933899] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Relation of diabetes mellitus (DM) to the various stages of corneal nerve fiber damage is well accepted. A possible association between changes in the cornea of diabetic patients and diabetic retinopathy (DR), DM duration, and age at the time of DM diagnosis were evaluated. The study included 60 patients with DM type 1 (DM1) and 20 healthy control subjects. The density of basal epithelial cells, keratocytes and endothelial cells, and the status of the subbasal nerve fibers were evaluated using in vivo corneal confocal microscopy. Basal epithelial cell density increased with age (p=0.026), while stromal and endothelial cell density decreased with age (p=0.003, p=0.0005, p<0.0001). After the DM1 diagnosis was established, this association with age weaken. We showed nerve fiber damage in DM1 patients (p˂0.0001). The damage correlated with the degree of DR. DM1 patients with higher age at DM1 diagnosis had a higher nerve fiber density (p=0.0021). These results indicated that age at DM1 diagnosis potentially has an important effect on final nerve fiber and corneal cell density.
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Affiliation(s)
| | | | | | - G. MAHELKOVÁ
- Department of Ophthalmology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
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23
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Govindaswamy N, Gadde SG, Chidambara L, Bhanushali D, Anegondi N, Sinha Roy A. Quantitative evaluation of optical coherence tomography angiography images of diabetic retinopathy eyes before and after removal of projection artifacts. JOURNAL OF BIOPHOTONICS 2018; 11:e201800003. [PMID: 29660256 DOI: 10.1002/jbio.201800003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Accepted: 04/06/2018] [Indexed: 06/08/2023]
Abstract
Projection artifacts (PAs) affect the quantification of vascular parameters in the deep layer optical coherence tomography (OCT) angiography image. This study eliminated PA and quantified its effect on imaging. 53 eyes (30 subjects) of normal Indian subjects and 113 eyes (92 patients) of type 2 diabetes mellitus with retinopathy (DR) underwent imaging with a scan area of 3 mm × 3 mm. In this study, a normalized cross-correlation between superficial and deep layer was used to remove PA in deep layer. Local fractal analysis was done to compute vascular parameters such as foveal avascular zone area (mm2 ), vessel density (%), spacing between large vessels (%) and spacing between small vessels (%). Before PA removal, vessel density for mild nonproliferative (NPDR), moderate NPDR, severe NPDR and proliferative DR were 42.56 ±1.69%, 40.69 ±0.72%, 37.34 ±0.85% and 35.61 ±1.26%, respectively. After artifact removal, vessel density was 28.9 ±1.22%, 29.9 ±0.56%, 26.19 ±0.59% and 24.02 ±0.94%, respectively. All the vascular parameters were statistically significant (P <.001) between normal and disease eyes, irrespective of superficial and deep retinal layers. Parafoveal sectoral analyses showed that temporal zone had the lowest vessel density and may undergo DR-related changes first. The current approach enabled rapid and accurate quantitative interpretation of DR eyes, without PA.
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Affiliation(s)
- Nivedhitha Govindaswamy
- Imaging, Biomechanics and Mathematical Modeling Solutions, Narayana Nethralaya Foundation, Bangalore, India
| | - Santosh G Gadde
- Department of retina services, Narayana Nethralaya Eye Hospital, Bangalore, India
| | - Lavanya Chidambara
- Department of retina services, Narayana Nethralaya Eye Hospital, Bangalore, India
| | - Devanshi Bhanushali
- Department of retina services, Narayana Nethralaya Eye Hospital, Bangalore, India
| | - Neha Anegondi
- Imaging, Biomechanics and Mathematical Modeling Solutions, Narayana Nethralaya Foundation, Bangalore, India
| | - Abhijit Sinha Roy
- Imaging, Biomechanics and Mathematical Modeling Solutions, Narayana Nethralaya Foundation, Bangalore, India
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Sun H, Lee P, Yan C, Gao N, Wang J, Fan X, Yu FS. Inhibition of Soluble Epoxide Hydrolase 2 Ameliorates Diabetic Keratopathy and Impaired Wound Healing in Mouse Corneas. Diabetes 2018; 67:1162-1172. [PMID: 29615440 PMCID: PMC5961414 DOI: 10.2337/db17-1336] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2017] [Accepted: 03/17/2018] [Indexed: 12/18/2022]
Abstract
EPHX2 (encoding soluble epoxide hydrolase [sEH]) converts biologically active epoxyeicosatrienoic acids (EETs), anti-inflammatory and profibrinolytic effectors, into the less biologically active metabolites, dihydroxyeicostrienoic acids. We sought to characterize the expression and the function of EPHX2 in diabetic corneas and during wound healing. The expression of EPHX2 at both mRNA and protein levels, as well as sEH enzymatic activity, was markedly upregulated in the tissues/cells, including corneal epithelial cells as well as the retina of human type 2 and mouse type 1 (streptozotocin [STZ] induced) and/or type 2 diabetes. Ephx2 depletion had no detectable effects on STZ-induced hyperglycemia but prevented the development of tear deficiency. Ephx2-/- mice showed an acceleration of hyperglycemia-delayed epithelium wound healing. Moreover, inhibition of sEH increased the rate of epithelium wound closure and restored hyperglycemia-suppressed STAT3 activation and heme oxygenase-1 (HO-1) expression in the diabetic corneas. Treatment of diabetic corneas with cobalt protoporphyrin, a well-known HO-1 inducer, restored wound-induced HO-1 upregulation and accelerated delayed wound healing. Finally, Ephx2 depletion enhanced sensory innervation and regeneration in diabetic corneas at 1 month after epithelial debridement. Our data suggest that increased sEH activity may be a contributing factor for diabetic corneal complications; targeting sEH pharmacologically or supplementing EETs may represent a new, adjunctive therapy for treating diabetic keratopathy.
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Affiliation(s)
- Haijing Sun
- Departments of Ophthalmology and Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI
| | - Patrick Lee
- Departments of Ophthalmology and Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI
| | - Chenxi Yan
- Departments of Ophthalmology and Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI
- Department of Ophthalmology, Shanghai Ninth Peoples' Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Nan Gao
- Departments of Ophthalmology and Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI
| | - Jiemei Wang
- Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI
| | - Xianqun Fan
- Department of Ophthalmology, Shanghai Ninth Peoples' Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
| | - Fu-Shin Yu
- Departments of Ophthalmology and Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI
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Ma A, Mak MS, Shih KC, Tsui CK, Cheung RK, Lee SH, Leung H, Leung JN, Leung JT, Van-Boswell MZ, Wong MT, Ng ALK, Lee CH, Jhanji V, Tong L. Association of long-term glycaemic control on tear break-up times and dry eye symptoms in Chinese patients with type 2 diabetes. Clin Exp Ophthalmol 2018; 46:608-615. [PMID: 29345402 DOI: 10.1111/ceo.13146] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Revised: 01/04/2018] [Accepted: 01/08/2018] [Indexed: 12/21/2022]
Abstract
IMPORTANCE Diabetes mellitus is known to be associated with dry eye syndrome (DES), but the effects of long-term glycaemic control on tear film metrics and dry eye symptoms are not known in the Chinese population. BACKGROUND To evaluate tear film stability and dry eye symptoms and their associations with systemic risk factors in Chinese patients with type 2 diabetes mellitus (T2DM). DESIGN Cross-sectional study set at the Lo Fong Siu Po Eye Centre (Grantham Hospital), Hong Kong. PARTICIPANTS A total of 80 Chinese participants, aged 18 or above, with T2DM recruited from the specialist outpatient setting were included. METHODS The Oculus Keratograph 5M (Oculus Inc., Wetzlar, Germany) was used to measure the non-invasive tear break-up time (NITBUT). Ocular symptoms were evaluated using the Ocular Surface Disease Index (OSDI). The association between OSDI, NITBUT and metabolic parameters relating to diabetes were evaluated using multiple linear regression. MAIN OUTCOME MEASURES The associations between long-term glycaemic control and NITBUT and OSDI scores. RESULTS Stepwise multiple linear regression analysis revealed glycated haemoglobin to be the only significant independent variable for NITBUT (R2 = 0.099, P = 0.014) and OSDI (R2 = 0.062, P = 0.044) after controlling for potential confounders. The age-adjusted prevalence of DES was 20% (95% confidence interval: 11-30%) in the Chinese T2DM population. The odds of DES for increasing percentage of glycated haemoglobin was 1.49 (95% confidence interval: 1.03-2.17, P = 0.04). CONCLUSIONS AND RELEVANCE Our findings highlight the importance of good glycaemic control as a modifiable risk factor for both dry eye symptoms and tear film instability in patients with T2DM.
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Affiliation(s)
- Andre Ma
- Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong
| | - Martin Sy Mak
- Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong
| | - Kendrick Co Shih
- Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.,Lo Fong Siu Po Eye Centre, Grantham Hospital, Aberdeen, Hong Kong
| | - Claudia Ky Tsui
- Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong
| | - Rachel Ky Cheung
- Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong
| | - Sherman H Lee
- Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong
| | - Hubert Leung
- Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong
| | - Joyce Ns Leung
- Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong
| | - Jason Th Leung
- Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong
| | - Marco Z Van-Boswell
- Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong
| | - Michael Tl Wong
- Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong
| | - Alex Lap-Ki Ng
- Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.,Lo Fong Siu Po Eye Centre, Grantham Hospital, Aberdeen, Hong Kong
| | - Chi-Ho Lee
- Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.,KK Leung Diabetes Centre, Queen Mary Hospital, Pokfulam, Hong Kong
| | - Vishal Jhanji
- Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Louis Tong
- Ocular Surface Research Group, Singapore Eye Research Institute, Singapore.,Corneal and External Eye Disease Service, Singapore National Eye Centre, Singapore.,Eye-Academic Clinical Program, Duke-NUS Medical School, Singapore.,Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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Wojnar W, Kaczmarczyk-Sedlak I, Zych M. Diosmin ameliorates the effects of oxidative stress in lenses of streptozotocin-induced type 1 diabetic rats. Pharmacol Rep 2017; 69:995-1000. [DOI: 10.1016/j.pharep.2017.04.005] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Revised: 01/25/2017] [Accepted: 04/03/2017] [Indexed: 12/25/2022]
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Heitmar R, Lip GYH, Ryder RE, Blann AD. Retinal vessel diameters and reactivity in diabetes mellitus and/or cardiovascular disease. Cardiovasc Diabetol 2017; 16:56. [PMID: 28446234 PMCID: PMC5406879 DOI: 10.1186/s12933-017-0534-6] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2016] [Accepted: 04/11/2017] [Indexed: 12/27/2022] Open
Abstract
Background Retinal vessel calibre and vascular dilation/constriction in response to flicker light provocation may provide a measure distinguishing patients suffering from diabetes mellitus and/or cardiovascular disease. Methods One hundred and sixteen age and sex matched patients with diabetes mellitus (DM), cardiovascular disease (CVD) and both DM and CVD (DM + CVD) underwent systemic and intraocular pressure measurements. Retinal vessel calibres were assessed using a validated computer-based program to compute central retinal artery and vein equivalents (CRVE) from monochromatic retinal images. Vessel dilation and constriction responses to flicker light provocation were assessed by continuous retinal vessel diameter recordings. Plasma endothelial markers von Willebrand factor (vWf) and soluble E selectin (sEsel) were measured by ELISA. Results Retinal vessel calibres were comparable across groups but CRVE correlated significantly with disease duration in DM patients (r = 0.57, p < 0.001). Patients suffering DM only exhibited reduced arterial vasomotion at rest and reduced arterial constriction following flicker light induced vessel dilation compared to patients with CVD and those suffering both CVD + DM (p = 0.030). Patients suffering from CVD + DM exhibited significant differences between each flicker cycle in regards to arterial maximum constriction (p = 0.006) and time needed to reach arterial maximum dilation (p = 0.004), whereas the other two groups did not show such inconsistencies between individual flicker cycles. vWf was raised in CVD + DM compared to the other two groups (p ≤ 0.02), whilst sEsel was raised in CVD + DM compared to DM alone (p = 0.044). Conclusions Dynamic retinal vascular calibres as obtained by continuous diameter measurements using flicker light provocation can reveal subtle differences between groups suffering from CVD with and without DM. This difference in reaction pattern and lack of arterial constriction in DM may provide a suitable marker to monitor progression.
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Affiliation(s)
- R Heitmar
- School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET, UK.
| | - G Y H Lip
- School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, B4 7ET, UK.,Institute for Cardiovascular Sciences, University of Birmingham, City Hospital, Birmingham, B18 7QH, UK
| | - R E Ryder
- Department of Diabetes and Endocrinology, City Hospital, Birmingham, B18 7QH, UK
| | - A D Blann
- Institute for Cardiovascular Sciences, University of Birmingham, City Hospital, Birmingham, B18 7QH, UK
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Yakin M, Yalniz-Akkaya Z, Sevim-Yakin S, Balta O, Ornek F. Ophthalmologic evaluation in geriatric patients: Assessment of consistency between patients' complaints and ocular diagnoses. Arch Gerontol Geriatr 2016; 68:90-96. [PMID: 27710877 DOI: 10.1016/j.archger.2016.09.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2015] [Revised: 09/28/2016] [Accepted: 09/29/2016] [Indexed: 10/20/2022]
Abstract
PURPOSE This study aimed to assess the consistency between patients' complaints and their eye diseases. DESIGN Cross-sectional study. METHODS RESULTS: The frequencies of at least one newly diagnosed visually important ocular disease were 25.9%, 27.0%, and 45.3% in groups 1, 2, and 3, respectively (p<0.001). The same frequencies were significantly higher in patients >75 years of age compared with the younger group (59.1% vs. 22.0%, p<0.001). Although these values were statistically significant in patients ≤75 years of age (p<0.001), they were insignificant in patients >75 years of age according to type of complaints (p=0.773). Patients with diabetes mellitus exhibited significantly lower vision, higher rate of visually important ocular diseases, and higher intraocular pressure readings than patients without diabetes mellitus (p=0.009, 0.015, and 0.002, respectively). CONCLUSIONS Visually important ocular diseases were diagnosed approximately in a quarter of patients who had no complaints about decrease in vision and in more than half of the oldest geriatric patients (>75years) irrespective of the type of complaints.
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Affiliation(s)
- Mehmet Yakin
- Department of Ophthalmology, Ankara Training and Research Hospital, Altindag, Ankara, Turkey.
| | - Zuleyha Yalniz-Akkaya
- Department of Ophthalmology, Ankara Training and Research Hospital, Altindag, Ankara, Turkey
| | - Sultan Sevim-Yakin
- Department of Anesthesiology and Reanimation, Numune Training and Research Hospital, Altindag, Ankara, Turkey
| | - Ozgur Balta
- Department of Ophthalmology, Ankara Training and Research Hospital, Altindag, Ankara, Turkey
| | - Firdevs Ornek
- Department of Ophthalmology, Ankara Training and Research Hospital, Altindag, Ankara, Turkey
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Alvarez-Rivera F, Fernández-Villanueva D, Concheiro A, Alvarez-Lorenzo C. α-Lipoic Acid in Soluplus ® Polymeric Nanomicelles for Ocular Treatment of Diabetes-Associated Corneal Diseases. J Pharm Sci 2016; 105:2855-2863. [DOI: 10.1016/j.xphs.2016.03.006] [Citation(s) in RCA: 76] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2016] [Revised: 03/04/2016] [Accepted: 03/07/2016] [Indexed: 12/16/2022]
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Wang Y, Qin S, Pen G, Chen D, Han C, Miao C, Lu B, Su C, Feng S, Li W, Han J, Cho NC, Si Y. Original Research: Potential ocular protection and dynamic observation of Polygonatum sibiricum polysaccharide against streptozocin-induced diabetic rats' model. Exp Biol Med (Maywood) 2016; 242:92-101. [PMID: 27510582 DOI: 10.1177/1535370216663866] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Accepted: 06/24/2016] [Indexed: 01/01/2023] Open
Abstract
Ocular complications associated with diabetes mellitus are progressive and becoming one of the most important causes of morbidity worldwide. The purpose of the study is to evaluate the protective effect of Polygonatum sibiricum polysaccharide, an important component of Polygonatum sibiricum, on ocular complications in streptozotocin-induced diabetes mellitus rats. Sprague Dawley rats were made diabetic with streptozotocin(60 mg/kg, i.v.) and then the rats were treated with Polygonatum sibiricum polysaccharide 200, 400 and 800 mg/kg.d by gavage for 12 weeks. Biochemical analysis indicated that Polygonatum sibiricum polysaccharide lowered the levels of fasting blood glucose and glycated hemoglobin in blood and elevated the levels of insulin and C-peptide in plasma of diabetes mellitus rats in a dose-dependent manner. Physical measurements revealed that Polygonatum sibiricum polysaccharide improved clinical symptoms of polydipsia, polyphagia, polyuria and weight loss in diabetes mellitus rats. The content of malondialdehyde and activity of superoxide dismutase in plasma were determined, and the data showed Polygonatum sibiricum polysaccharide suppressed oxidative stress reaction. Lens opacification was observed using slit lamp illumination, and the data showed Polygonatum sibiricum polysaccharide delayed cataract progression in a dose-dependent manner. Electroretinogram showed Polygonatum sibiricum polysaccharide treatment reversed the decrease of electroretinogram b and OPs2 waves' amplitudes. Flash-visual evoked potential test indicated that the peak time of P2 wave was prolonged, and the amplitude of N2-P2 was lowered in diabetes mellitus group, and Polygonatum sibiricum polysaccharide suppressed these changes. Fundus fluorescein angiography showed Polygonatum sibiricum polysaccharide alleviated the retinal vasculopathy in a dose-dependent manner. In conclusion, these results suggest that the administration of Polygonatum sibiricum polysaccharide slows the progression of diabetic retinopathy and cataract through alleviating hyperglycemia and reducing oxidative stress in streptozotocin-induced diabetes mellitus rats.
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Affiliation(s)
- Yi Wang
- Department of Ophthalmology, Chonbuk National University, Jeollabuk-do 561-756, Republic of Korea (past position).,Department of Ophthalmology, Affiliated Hospital of Taishan Medical University, Taian 271000, China
| | - Shucun Qin
- Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Taian 271000, China
| | - Guoqing Pen
- Department of Ophthalmology, Affiliated Hospital of Taishan Medical University, Taian 271000, China
| | - Di Chen
- Department of Ophthalmology, Affiliated Hospital of Taishan Medical University, Taian 271000, China
| | - Chao Han
- Department of Ophthalmology, Affiliated Hospital of Taishan Medical University, Taian 271000, China
| | - Chunrun Miao
- Department of Ophthalmology, Affiliated Hospital of Taishan Medical University, Taian 271000, China
| | - Baojin Lu
- Department of Ophthalmology, Affiliated Hospital of Taishan Medical University, Taian 271000, China
| | - Chao Su
- Department of Ophthalmology, Affiliated Hospital of Taishan Medical University, Taian 271000, China
| | - Shanlong Feng
- Department of Ophthalmology, Affiliated Hospital of Taishan Medical University, Taian 271000, China
| | - Wen Li
- Department of Ophthalmology, Affiliated Hospital of Taishan Medical University, Taian 271000, China
| | - Jingjing Han
- Department of Ophthalmology, Affiliated Hospital of Taishan Medical University, Taian 271000, China
| | - Nam C Cho
- Department of Ophthalmology, Chonbuk National University, Jeollabuk-do 561-756, Republic of Korea (past position)
| | - Yanhong Si
- Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Taian 271000, China
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Daull P, Feraille L, Elena PP, Garrigue JS. Comparison of the Anti-Inflammatory Effects of Artificial Tears in a Rat Model of Corneal Scraping. J Ocul Pharmacol Ther 2016; 32:109-18. [PMID: 26751507 PMCID: PMC4779975 DOI: 10.1089/jop.2015.0054] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Accepted: 10/19/2015] [Indexed: 01/10/2023] Open
Abstract
PURPOSE Artificial tears (ATs) are used routinely to alleviate the symptoms of mild to moderate dry eye. Preservative-free cationic emulsions (eg, Cationorm(®)) are an innovative approach for the management of signs and symptoms of dry eye. The aim of the present exploratory experiment was to evaluate the efficacy of this cetalkonium chloride (CKC)-containing cationic emulsion on debrided cornea and to characterize its effects on scraping-induced inflammation. METHODS Four ATs were assessed in a rat model of corneal scraping. The upper part of the corneal epithelium was scraped before a 5-day treatment, followed by clinical evaluations and fluorescein staining to evaluate cornea recovery. The anti-inflammatory efficacy of the ATs was assessed in vivo and in vitro. RESULTS In vivo confocal microscopy (IVCM) revealed a trend toward better corneal clinical signs (lower IVCM scores) for the animals treated with the unpreserved ATs. Benzalkonium chloride treatment decreased goblet cell count by 37.5%. While the soft-preserved Systane Balance(®) and Optive(®) and the preservative-free Vismed(®) had no effect on the goblet cell count, Cationorm increased this count by almost 40%. Interestingly, inflammatory cell infiltration in the stroma was at its lowest following treatment with the preservative-free Cationorm. Cationorm is also the only AT decreasing IL6- and IL8-stimulated secretion by 59% and 74%, respectively. CONCLUSION By restoring an adequately hydrated ocular surface environment, the different ATs promote corneal epithelium healing. These data position Cationorm as a promising AT for the management of signs and symptoms of dry eye in patients with mild to moderate dry eye disease presenting chronic subclinical levels of ocular inflammation.
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Sun H, Mi X, Gao N, Yan C, Yu FS. Hyperglycemia-suppressed expression of Serpine1 contributes to delayed epithelial wound healing in diabetic mouse corneas. Invest Ophthalmol Vis Sci 2015; 56:3383-92. [PMID: 26024123 DOI: 10.1167/iovs.15-16606] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
PURPOSE Patients with diabetes mellitus (DM) are at an increased risk for developing corneal complications, including delayed wound healing. The purpose of this study was to characterize the expression and the function of Serpine1 and other components of urokinase plasminogen activator (uPA)-proteolytic system in delayed epithelial wound healing in diabetic mouse corneas. METHODS Mice of the strain C57BL/6 were induced to develop diabetes by streptozotocin, and wound-healing assays were performed 10 weeks afterward. Gene expression and/or distribution were assessed by real-time PCR, Western blotting, and/or immunohistochemistry. The role of Serpine1 in mediating epithelial wound closure was determined by subconjunctival injections of neutralizing antibodies in either normal or recombinant protein in diabetic corneas. Enzyme assay for matrix metalloproteinase (MMP)-3 was also performed. RESULTS The expressions of Serpine1 (PAI-1), Plau (uPA), and Plaur (uPA receptor) were upregulated in response to wounding, and these upregulations were significantly suppressed by hyperglycemia. In healing epithelia, Plau and Serpine1 were abundantly expressed at the leading edge of the healing epithelia of normal and, to a lesser extent, diabetic corneas. Inhibition of Serpine1 delayed epithelial wound closure in normal corneas, whereas recombinant Serpine1 accelerated it in diabetic corneas. The Plau and MMP-3 mRNA levels and MMP-3 enzymatic activities were correlated to Serpine1 levels and/or the rates of epithelial wound closure. CONCLUSIONS Serpine1 plays a role in mediating epithelial wound healing and its impaired expression may contribute to delayed wound healing in DM corneas. Hence, modulating uPA proteolytic pathway may represent a new approach for treating diabetic keratopathy.
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TNF-related apoptosis inducing ligand in ocular cancers and ocular diabetic complications. BIOMED RESEARCH INTERNATIONAL 2015; 2015:424019. [PMID: 25834817 PMCID: PMC4365302 DOI: 10.1155/2015/424019] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/19/2015] [Accepted: 02/17/2015] [Indexed: 01/06/2023]
Abstract
TNF-related apoptosis inducing ligand (TRAIL) is an intensively studied cytokine, in particular for its anticancer activity. The discovery that conjunctival sac fluid contains extremely high levels of soluble TRAIL as compared to other body fluids suggested important implications in the context of the immunological surveillance of the eye, in particular of the anterior surface. In this review, we discuss the potential physiopathologic and therapeutic role of the TRAIL/TRAIL receptor system in a variety of ocular cancers. Moreover, since an increasing amount of data has indicated the important biological activities of the TRAIL/TRAIL receptor systems also in a completely different pathologic context such as diabetes mellitus, in the second part of this review we summarize the currently available data on the involvement of TRAIL in the ocular complications of diabetes mellitus as modulator of the inflammatory and angiogenic response in the eye.
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Sayin N, Kara N, Pekel G. Ocular complications of diabetes mellitus. World J Diabetes 2015; 6:92-108. [PMID: 25685281 PMCID: PMC4317321 DOI: 10.4239/wjd.v6.i1.92] [Citation(s) in RCA: 180] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2014] [Revised: 10/06/2014] [Accepted: 12/10/2014] [Indexed: 02/05/2023] Open
Abstract
Diabetes mellitus (DM) is a important health problem that induces ernestful complications and it causes significant morbidity owing to specific microvascular complications such as, retinopathy, nephropathy and neuropathy, and macrovascular complications such as, ischaemic heart disease, and peripheral vasculopathy. It can affect children, young people and adults and is becoming more common. Ocular complications associated with DM are progressive and rapidly becoming the world’s most significant cause of morbidity and are preventable with early detection and timely treatment. This review provides an overview of five main ocular complications associated with DM, diabetic retinopathy and papillopathy, cataract, glaucoma, and ocular surface diseases.
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Paolini P, Pick D, Lapira J, Sannino G, Pasqualini L, Ludka C, Sprague LJ, Zhang X, Bartolotta EA, Vazquez-Hidalgo E, Barba DT, Bazan C, Hardiman G. Developmental and extracellular matrix-remodeling processes in rosiglitazone-exposed neonatal rat cardiomyocytes. Pharmacogenomics 2015; 15:759-74. [PMID: 24897284 DOI: 10.2217/pgs.14.39] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVE The objective of this study was to investigate the effects of rosiglitazone (Avandia(®)) on gene expression in neonatal rat ventricular myocytes. MATERIALS & METHODS Myocytes were exposed to rosiglitazone ex vivo. The two factors examined in the experiment were drug exposure (rosiglitazone and dimethyl sulfoxide vs dimethyl sulfoxide), and length of exposure to drug (½ h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 18 h, 24 h, 36 h and 48 h). RESULTS Transcripts that were consistently expressed in response to the drug were identified. Cardiovascular system development, extracellular matrix and immune response are represented prominently among the significantly modified gene ontology terms. CONCLUSION Hmgcs2, Angptl4, Cpt1a, Cyp1b1, Ech1 and Nqo1 mRNAs were strongly upregulated in cells exposed to rosiglitazone. Enrichment of transcripts involved in cardiac muscle cell differentiation and the extracellular matrix provides a panel of biomarkers for further analysis in the context of adverse cardiac outcomes in humans. Original submitted 15 November 2013; Revision submitted 14 February 2014.
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Affiliation(s)
- Paul Paolini
- Department of Biology, San Diego State University, CA, USA
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Scientometric Analysis and Mapping of Scientific Articles on Diabetic Retinopathy. MEDICAL HYPOTHESIS, DISCOVERY & INNOVATION OPHTHALMOLOGY JOURNAL 2015; 4:81-100. [PMID: 27350949 PMCID: PMC4921208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Diabetic retinopathy (DR) is the major cause of blindness among the working-age population globally. No systematic research has been previously performed to analyze the research published on DR, despite the need for it. This study aimed to analyze the scientific production on DR to draw overall roadmap of future research strategic planning in this field. A bibliometric method was used to obtain a view on the scientific production about DR by the data extracted from the Institute for Scientific Information (ISI). Articles about DR published in 1993-2013 were analyzed to obtain a view of the topic's structure, history, and to document relationships. The trends in the most influential publications and authors were analyzed. Most highly cited articles addressed epidemiologic and translational research topics in this field. During the past 3 years, there has been a trend toward biomarker discovery and more molecular translational research. Areas such as gene therapy and micro-RNAs are also among the recent hot topics. Through analyzing the characteristics of papers and the trends in scientific production, we performed the first scientometric report on DR. Most influential articles have addressed epidemiology and translational research subjects in this field, which reflects that globally, the earlier diagnosis and treatment of this devastating disease still has the highest global priority.
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Shen Y, Wen Z, Wang N, Zheng Z, Liu K, Xia X, Gu Q, Shi Y, Xu X. Investigation of variants in UCP2 in Chinese type 2 diabetes and diabetic retinopathy. PLoS One 2014; 9:e112670. [PMID: 25396419 PMCID: PMC4232517 DOI: 10.1371/journal.pone.0112670] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2014] [Accepted: 10/10/2014] [Indexed: 12/11/2022] Open
Abstract
Purpose The aim of this study was to investigate variants in UCP2 genes in type 2 diabetes mellitus (DM) and diabetic retinopathy (DR) in Chinese population. Materials and Methods We conducted a single nucleotide polymorphism-based and haplotype-based case-control study between the variants of UCP2 and DM and between the variants of UCP2 and DR in 479 Chinese patients with type 2 DM and 479 control subjects without DM. Two SNPs (rs660339 and rs659366) were selected as genetic markers. Results The risk allele C at UCP2 rs660339 was closely associated with DM in Chinese population. There was significant difference in rs660339 between DM and controls (P = 0.0016; OR [95%CI] = 1.37 (1.14–1.65)). Subjects who were homozygous of the C allele were more likely to develop DM. The frequency of C allele was higher in DM (58%) than in control (51%). But this locus didn't have a definite effect on the onset of non-proliferative diabetic retinopathy (NPDR) (P = 0.44; OR [95%CI] = 0.80 (0.56–1.14)) and proliferative diabetic retinopathy (PDR) (P = 1.00; OR [95%CI] = 0.99 (0.74–1.34)) comparing to subjects with DM without retinopathy (DWR), respectively. Moreover, the UCP2 rs659366 polymorphism showed no significant difference between DM and control (P = 0.66; OR [95%CI] = 1.10 (0.91–1.32)). However, there was a significant difference between PDR and DWR (P = 0.016; OR [95%CI] = 0.66 (0.49–0.90)), but there was no difference between NPDR and DWR (P = 1.00; OR [95%CI] = 0.96 (0.67–1.37)). Participants who carried the G allele at rs659366 were more likely to develop PDR. For the haplotype, C-A was present more frequently in DM than in control (16% vs 7%), indicating that it was risky, and T-A was present less in DM than in control (29% vs 35%). Haplotype frequencies in DR and DWR showed no significant difference (P = 0.068). Conclusion It was indicated that UCP2 may be implicated in the pathogenesis of type 2 DM and DR in Chinese population.
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Affiliation(s)
- Yinchen Shen
- Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China, Shanghai Key Laboratory of Fundus Disease, Shanghai, People's Republic of China
| | - Zujia Wen
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, People's Republic of China
| | - Ning Wang
- Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China, Shanghai Key Laboratory of Fundus Disease, Shanghai, People's Republic of China
- * E-mail:
| | - Zhi Zheng
- Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China, Shanghai Key Laboratory of Fundus Disease, Shanghai, People's Republic of China
| | - Kun Liu
- Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China, Shanghai Key Laboratory of Fundus Disease, Shanghai, People's Republic of China
| | - Xin Xia
- Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China, Shanghai Key Laboratory of Fundus Disease, Shanghai, People's Republic of China
| | - Qing Gu
- Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China, Shanghai Key Laboratory of Fundus Disease, Shanghai, People's Republic of China
| | - Yongyong Shi
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, People's Republic of China
| | - Xun Xu
- Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, People's Republic of China, Shanghai Key Laboratory of Fundus Disease, Shanghai, People's Republic of China
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He H, Williams-Guy K, Pagadala J, Presley CS, Miller DD, Steinle JJ, Yates CR. A sensitive and fast LC-MS/MS method for determination of β-receptor agonist JP-49b: application to a pharmacokinetic study in rats. J Chromatogr B Analyt Technol Biomed Life Sci 2014; 953-954:86-91. [PMID: 24576769 DOI: 10.1016/j.jchromb.2014.01.031] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2013] [Revised: 01/17/2014] [Accepted: 01/22/2014] [Indexed: 10/25/2022]
Abstract
Ocular administration of the beta (β)-adrenergic receptor agonist JP-49b prevents retinopathy-like damage in a preclinical rat model of diabetes. Importantly, JP-49b did not induce characteristic β-adrenergic agonist-related side effects (e.g., left ventricular damage), which led to the hypothesis that JP-49b systemic exposure was minimal following ocular administration. To test this hypothesis, a sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed to study the preclinical pharmacokinetics of JP-49b in rats. Animals received either a single periocular or intravenous injection of JP-49b (10mg/kg) and plasma and tissue samples were obtained. JP-49b and fenoterol hydrobromide (internal standard, IS) were isolated by liquid-liquid extraction and extracts were analyzed by reversed-phase liquid chromatography on a C18 column using a gradient elution (acetic acid in water and methanol). A triple quadrupole mass spectrometer operating in the positive electrospray ionization mode with multiple reaction monitoring was used to detect JP-49b and IS transitions of m/z 346.4→195.1 and 304.1→134.9. The method was validated for selectivity, linearity, accuracy, and precision in rat vitreous humor, tissue homogenates, and plasma. Following intravenous administration, JP-49b was found to have a rapid clearance (36±5.8L/h/kg), high volume of distribution (244±51.5L/kg) and a terminal half-life of 4.8±1.6h. JP-49b was rapidly absorbed and extensively distributed into ocular tissue following topical administration. However, JP-49b was undetectable in heart tissue 24h after ocular administration. High local drug concentrations coupled with minimal systemic exposure following ocular administration supports further testing of JP-49b as a localized therapy for diabetic retinopathy.
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Affiliation(s)
- Hui He
- Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, United States
| | - Kimberly Williams-Guy
- Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN 38163, United States
| | - Jayaprakash Pagadala
- Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, United States
| | - Chaela Sickbert Presley
- Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, United States
| | - Duane D Miller
- Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, United States
| | - Jena J Steinle
- Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, United States; Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN 38163, United States; Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, United States
| | - Charles R Yates
- Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, United States; Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN 38163, United States.
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