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Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium. Mol Neurodegener 2023 Sep 21;18(1):64

Date

09/22/2023

Pubmed ID

37735444

Pubmed Central ID

PMC10514988

DOI

10.1186/s13024-023-00655-y

Scopus ID

2-s2.0-85171956125 (requires institutional sign-in at Scopus site)   11 Citations

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.

Author List

Soucy JR, Aguzzi EA, Cho J, Gilhooley MJ, Keuthan C, Luo Z, Monavarfeshani A, Saleem MA, Wang XW, Wohlschlegel J, RReSTORe Consortium, Baranov P, Di Polo A, Fortune B, Gokoffski KK, Goldberg JL, Guido W, Kolodkin AL, Mason CA, Ou Y, Reh TA, Ross AG, Samuels BC, Welsbie D, Zack DJ, Johnson TV

Author

Matthew B. Veldman PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Brain
Cell Differentiation
Humans
Mammals
Optic Nerve Diseases
Retina
Retinal Ganglion Cells