TY - JOUR
T1 - Retinal ganglion cell repopulation for vision restoration in optic neuropathy
T2 - a roadmap from the RReSTORe Consortium
AU - The RReSTORe Consortium
AU - Soucy, Jonathan R.
AU - Aguzzi, Erika A.
AU - Cho, Julie
AU - Gilhooley, Michael James
AU - Keuthan, Casey
AU - Luo, Ziming
AU - Monavarfeshani, Aboozar
AU - Saleem, Meher A.
AU - Wang, Xue Wei
AU - Wohlschlegel, Juilette
AU - Baranov, Petr
AU - Di Polo, Adriana
AU - Fortune, Brad
AU - Gokoffski, Kimberly K.
AU - Goldberg, Jeffrey L.
AU - Guido, William
AU - Kolodkin, Alex L.
AU - Mason, Carol A.
AU - Ou, Yvonne
AU - Reh, Thomas A.
AU - Ross, Ahmara G.
AU - Samuels, Brian C.
AU - Welsbie, Derek
AU - Zack, Donald J.
AU - Johnson, Thomas V.
AU - Fouda, Abdelrahman Y.
AU - Ashok, Ajay
AU - Moshiri, Ala
AU - Chedotal, Alain
AU - Reed, Amberlynn A.
AU - Askary, Amjad
AU - Su, An Jey A.
AU - La Torre, Anna
AU - Jalligampala, Archana
AU - Silva-Lepe, Ariadna
AU - Das, Arupratan
AU - Wirostko, Barbara
AU - Frankfort, Benjamin J.
AU - Sivyer, Benjamin
AU - Alapure, Bhagwat
AU - Young, Brent
AU - Clark, Brian
AU - Jones, Bryan William
AU - Hellmer, Chase
AU - Mitchell, Claire
AU - Ufongene, Claire
AU - Goldman, Dan
AU - Feldheim, David
AU - Gutmann, David H.
AU - Todd, Levi
N1 - Publisher Copyright: © 2023, Editorial Group and BioMed Central Ltd., part of Springer Nature.
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
KW - Glaucoma
KW - Neuroprotection
KW - Ophthalmology
KW - Optic neuropathy
KW - Organoids
KW - Regenerative medicine
KW - Retinal ganglion cells
KW - Stem cells
KW - Transplantation
UR - https://www.scopus.com/pages/publications/85171956125
U2 - 10.1186/s13024-023-00655-y
DO - 10.1186/s13024-023-00655-y
M3 - Review article
C2 - 37735444
SN - 1750-1326
VL - 18
JO - Molecular Neurodegeneration
JF - Molecular Neurodegeneration
IS - 1
M1 - 64
ER -