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Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium

Authors :
Jonathan R. Soucy
Erika A. Aguzzi
Julie Cho
Michael James Gilhooley
Casey Keuthan
Ziming Luo
Aboozar Monavarfeshani
Meher A. Saleem
Xue-Wei Wang
Juilette Wohlschlegel
The RReSTORe Consortium
Petr Baranov
Adriana Di Polo
Brad Fortune
Kimberly K. Gokoffski
Jeffrey L. Goldberg
William Guido
Alex L. Kolodkin
Carol A. Mason
Yvonne Ou
Thomas A. Reh
Ahmara G. Ross
Brian C. Samuels
Derek Welsbie
Donald J. Zack
Thomas V. Johnson
Source :
Molecular Neurodegeneration, Vol 18, Iss 1, Pp 1-46 (2023)
Publication Year :
2023
Publisher :
BMC, 2023.

Abstract

Abstract Retinal ganglion cell (RGC) death in glaucoma and other optic neuropathies results in irreversible vision loss due to the mammalian central nervous system’s limited regenerative capacity. RGC repopulation is a promising therapeutic approach to reverse vision loss from optic neuropathies if the newly introduced neurons can reestablish functional retinal and thalamic circuits. In theory, RGCs might be repopulated through the transplantation of stem cell-derived neurons or via the induction of endogenous transdifferentiation. The RGC Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) Consortium was established to address the challenges associated with the therapeutic repair of the visual pathway in optic neuropathy. In 2022, the RReSTORe Consortium initiated ongoing international collaborative discussions to advance the RGC repopulation field and has identified five critical areas of focus: (1) RGC development and differentiation, (2) Transplantation methods and models, (3) RGC survival, maturation, and host interactions, (4) Inner retinal wiring, and (5) Eye-to-brain connectivity. Here, we discuss the most pertinent questions and challenges that exist on the path to clinical translation and suggest experimental directions to propel this work going forward. Using these five subtopic discussion groups (SDGs) as a framework, we suggest multidisciplinary approaches to restore the diseased visual pathway by leveraging groundbreaking insights from developmental neuroscience, stem cell biology, molecular biology, optical imaging, animal models of optic neuropathy, immunology & immunotolerance, neuropathology & neuroprotection, materials science & biomedical engineering, and regenerative neuroscience. While significant hurdles remain, the RReSTORe Consortium’s efforts provide a comprehensive roadmap for advancing the RGC repopulation field and hold potential for transformative progress in restoring vision in patients suffering from optic neuropathies.

Details

Language :
English
ISSN :
17501326
Volume :
18
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Molecular Neurodegeneration
Publication Type :
Academic Journal
Accession number :
edsdoj.0496dd9029ef4175a2c853ac2f6e61b3
Document Type :
article
Full Text :
https://doi.org/10.1186/s13024-023-00655-y