Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Dec 15, 2018; 9(12): 239-251
Published online Dec 15, 2018. doi: 10.4239/wjd.v9.i12.239
Pathological changes in the cellular structures of retina and choroidea in the early stages of alloxan-induced diabetes
Irina Danilova, Svetlana Medvedeva, Svetlana Shmakova, Margarita Chereshneva, Alexey Sarapultsev, Petr Sarapultsev
Irina Danilova, Svetlana Medvedeva, Svetlana Shmakova, Department of Biology and Fundamental Medicine, Institute of Natural Sciences and Mathematics, Ural Federal University Named After the First Pres. of Russia B.N. Yeltsin, Ekaterinburg 620002, Russia
Irina Danilova, Svetlana Medvedeva, Svetlana Shmakova, Laboratory of Morphology and Biochemistry, Institute of Immunology and Physiology, Ural Division of Russian Academy of Sciences, Ekaterinburg 620049, Russia
Margarita Chereshneva, Laboratory of Immunophysiology and Immunopharmacology, Institute of Immunology and Physiology, Ural Division of Russian Academy of Sciences, Ekaterinburg 620049, Russia
Alexey Sarapultsev, Petr Sarapultsev, Institute of Chemical Engineering, Ural Federal University Named After the First Pres. of Russia B.N. Yeltsin, Ekaterinburg 620002, Russia
Alexey Sarapultsev, Petr Sarapultsev, Laboratory of Immunophatophysiology, Institute of Immunology and Physiology, Ural Division of Russian Academy of Sciences, Ekaterinburg 620049, Russia
Author contributions: Danilova I, Chereshneva M, Sarapultsev P, and Sarapultsev A contributed to the conception of the manuscript, design of experiments, and analysis and interpretation of the data, and wrote the manuscript; Danilova I, Medvedeva S, Shmakova S, and Sarapultsev A performed the experiments, analyzed the data, and wrote the manuscript; all authors have commented on the initial and final drafts of the manuscript and are responsible for approval of the final version of the manuscript in all aspects.
Supported by the Russian Science Foundation, No. 16-15-00039.
Institutional review board statement: This study protocol was reviewed and approved by the Institutional Review Board of Institute of Immunology and Physiology of Ural Branch of RAS, Ekaterinburg, Russia.
Institutional animal care and use committee statement: All institutional and national guidelines for the care and use of laboratory animals were followed. All experimental procedures with the animals were approved by the Institute of Animal Care and Use Committee at the Institute of Immunology and Physiology of the Ural Division of RAS (diab-1-04-2016).
Conflict-of-interest statement: The authors declare that there is no conflict of interest regarding the publication of this paper.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author to: Alexey Sarapultsev, MD, PhD, Senior Researcher, Laboratory of Immunophatophysiology, Institute of Immunology and Physiology, Ural Division of Russian Academy of Sciences, 106 Pervomayskaya Street, Ekaterinburg 620049, Russia. a.sarapultsev@gmail.com
Telephone: +7-343-3740070 Fax: +7-343-3740070
Received: June 26, 2018
Peer-review started: June 26, 2018
First decision: July 19, 2018
Revised: September 1, 2018
Accepted: November 2, 2018
Article in press: November 3, 2018
Published online: December 15, 2018
Processing time: 171 Days and 12 Hours
Abstract
AIM

To investigate the temporal sequence of pathological changes in the cellular structures of retina and choroidea in the early stages of diabetes in laboratory animals.

METHODS

Experimental type 1 diabetes was modeled by three intraperitoneal injections of an alloxan solution into 30 male nonlinear rats at 16 wk of age. The 30th and 60th days from the final alloxan injection were chosen as the endpoints. Light and electron microscopy and morphometric and immunohistochemical studies were performed on histological slices of eyeballs from experimental animals.

RESULTS

Diabetic disturbances progressed to 60 d of the experiment. Thus, in the retina, a partial destruction of photoreceptors accompanied by interstitial edema was observed. The morphometric analysis revealed a reduction in the thickness of the retina. A reduction in the number of blood vessels of the choroid with disturbances of the endothelial cells and the vascular walls and a persistent reduction in the number of melanocytes were observed. The number of proliferating Ki-67 positive cells decreased, and the number of macrophages increased with diabetes development.

CONCLUSION

The starting point in the development of destructive changes involves early reduction in the number of melanocytes of the choroidea and alterations in the retinal pigment epithelium.

Keywords: Alloxan; Diabetes; Diabetic retinopathy; Early stage; Morphology; Histological changes

Core tip: Diabetic retinopathy is the most frequent microvascular complication of diabetes. However, most of therapeutic approaches being developed do not address the early and potentially reversible failure of retinal perfusion. Thus, we examined pathological changes in the cellular structures of retina and choroidea in the early stages of diabetes in laboratory animals. According to the obtained results, the starting point in the development of destructive changes involves the early reduction in the number of melanocytes of the choroidea and the destruction of the retinal pigment epithelium, accompanied by an inflammatory process, which may represent a potential therapeutic target.