Review
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Jun 18, 2024; 14(2): 95009
Published online Jun 18, 2024. doi: 10.5500/wjt.v14.i2.95009
Whole-eye transplantation: Current challenges and future perspectives
Anna Scarabosio, Pier Luigi Surico, Vlad Tereshenko, Rohan Bir Singh, Carlo Salati, Leopoldo Spadea, Glenda Caputo, Pier Camillo Parodi, Caterina Gagliano, Jonathan M Winograd, Marco Zeppieri
Anna Scarabosio, Glenda Caputo, Pier Camillo Parodi, Department of Plastic Surgery, University Hospital of Udine, Udine 33100, Italy
Anna Scarabosio, Vlad Tereshenko, Jonathan M Winograd, Department of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States
Pier Luigi Surico, Rohan Bir Singh, Schepens Eye Research Institute of Mass Eye and Ear, Harvard Medical School, Boston, MA 02114, United States
Carlo Salati, Marco Zeppieri, Department of Ophthalmology, University Hospital of Udine, Udine 33100, Italy
Leopoldo Spadea, Eye Clinic, Policlinico Umberto I, "Sapienza" University of Rome, Rome 00142, Italy
Caterina Gagliano, Department of Medicine and Surgery, University of Enna "Kore", Enna 94100, Italy
Caterina Gagliano, Eye Clinic Catania University San Marco Hospital, Viale Carlo Azeglio Ciampi 95121 Catania, Italy
Co-first authors: Anna Scarabosio and Pier Luigi Surico.
Author contributions: Scarabosio A and Surico PL contributed equally as co-first authors; Scarabosio A, Surico PL, Salati C, Parodi PC, Leopoldo S and Zeppieri M wrote the outline; Scarabosio A, Surico PL did the research and writing of the manuscript; Salati C, Parodi PC, Spadea L, Tereshenko V, Singh RB, Caputo G, Winograd J Zeppieri M assisted in the writing of the paper; Scarabosio A, Surico PL, Zeppieri M were responsible for the conception and design of the study and Zeppieri M completed the English and scientific editing; Scarabosio A, Surico PL, Tereshenko V, Singh RB, Salati C, Caputo G, Parodi PC, Spadea S, Gagliano, Winograd J and Zeppieri M assisted in the editing and making critical revisions of the manuscript; all authors provided the final approval of the article.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Marco Zeppieri, MD, PhD, Doctor, Department of Ophthalmology, University Hospital of Udine, p.le S. Maria della Misericordia 15, Udine 33100, Italy. mark.zeppieri@asufc.sanita.fvg.it
Received: March 29, 2024
Revised: April 24, 2024
Accepted: May 15, 2024
Published online: June 18, 2024
Processing time: 76 Days and 12.6 Hours
Abstract

Whole-eye transplantation emerges as a frontier in ophthalmology, promising a transformative approach to irreversible blindness. Despite advancements, formidable challenges persist. Preservation of donor eye viability post-enucleation necessitates meticulous surgical techniques to optimize retinal integrity and ganglion cell survival. Overcoming the inhibitory milieu of the central nervous system for successful optic nerve regeneration remains elusive, prompting the exploration of neurotrophic support and immunomodulatory interventions. Immunological tolerance, paramount for graft acceptance, confronts the distinctive immunogenicity of ocular tissues, driving research into targeted immunosuppression strategies. Ethical and legal considerations underscore the necessity for stringent standards and ethical frameworks. Interdisciplinary collaboration and ongoing research endeavors are imperative to navigate these complexities. Biomaterials, stem cell therapies, and precision immunomodulation represent promising avenues in this pursuit. Ultimately, the aim of this review is to critically assess the current landscape of whole-eye transplantation, elucidating the challenges and advancements while delineating future directions for research and clinical practice. Through concerted efforts, whole-eye transplantation stands to revolutionize ophthalmic care, offering hope for restored vision and enhanced quality of life for those afflicted with blindness.

Keywords: Eye, Transplantation, Optic nerve, Nerve regeneration, Immunological tolerance

Core Tip: Whole-eye transplantation remains a theoretical endeavor. Innovative technologies like bioengineered eyes holding promise for future breakthroughs. The foremost challenge is to restore the functional connectivity between the optic nerve and the retina. The challenge of reconnecting the optic neural axis is explained by its peculiar anatomical features where the cell bodies of the sensory neurons are located within the retina itself. Regeneration of axonal populations within the optic nerve from the occipital cortex towards the retina is physiologically not feasible. Research in cell and animal models may provide new frontiers to overcome these functional hurdles, with hopes that eye-sight can be restored with eye transplantation.