Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium
Authors: Soucy Jonathan R. , Aguzzi Erika A. , Cho Julie , Gilhooley Michael James , Keuthan Casey , Luo Ziming , Monavarfeshani Aboozar , Saleem Meher A. , Wang Xue-Wei , Wohlschlegel Juilette ,   The RReSTORe Consortium, Fouda Abdelrahman Y. , Ashok Ajay , Moshiri Ala , Chedotal Alain , Reed Amberlynn A. , Askary Amjad , Su An-Jey A. , La Torre Anna , Jalligampala Archana , Silva-Lepe Ariadna , Das Arupratan , Wirostko Barbara , Frankfort Benjamin J. , Sivyer Benjamin , Alapure Bhagwat , Young Brent , Clark Brian , Jones Bryan William , Hellmer Chase , Mitchell Claire , Ufongene Claire , Goldman Dan , Feldheim David , Gutmann David H. , Calkins David J. , Krizaj David , Gamm David M. , Lozano Diana C. , Bovenkamp Diane E. , Chen Dong Feng , Cordero Elena Vecino , Trakhtenberg Ephraim F. , Tian Feng , Zhou Fengquan , McLellan Gillian J. , Quigley Harry A. , Serhan Hashem Abu , Tribble James R. , Meyer Jason , Gross Jeff , Mumm Jeff S. , Sivak Jeremy M. , Zhang Jingliang Simon , Do Jiun L. , Crowston Jonathan , Chen Julie , McGregor Juliette , Vinnakota Kalyan C. , Huang Kang-Chieh , Peynshaert Karen , Uyhazi Katherine E. , Martin Keith , Muller Ken , Park Kevin K. , Cho Kin-Sang , Chang Kun-Che , Benowitz Larry , Levin Leonard A. , Todd Levi , De Groef Lies , Moons Lieve , Alarcon-Martinez Luis , Singh Mandeep S. , Vidal-Sanz Manuel , Silveira Mariana S. , Pavlou Marina , Veldman Matthew B. , Van Hook Matthew , Samuel Melanie , Hu Mengming , Peng Micalla , Young Michael , Cayouette Michel , Geranmayeh Mohammad H. , Woodworth Mollie , Vetter Monica , Marsh-Armstrong Nicholas R. , Williams Pete A. , Rasiah Pratheepa Kumari , Subramanian Preeti , Cui Qi N. , Sappington Rebecca M. , Amine Reem , Eva Richard , Johnston Robert J. , Giger Roman J. , Ethier Ross , Abed Sadaf , Momin Sehrish Nizar Ali , Blackshaw Seth , Liddelow Shane A. , Mary Stella , Atolagbe Stephen , Varadarajan Supraja , Nabhan Tareq I. , Khatib Tasneem , Sharma Tasneem Putliwala , Brunner Thomas , Greenwell Tom , Rex Tonia S. , Watkins Trent , Badea Tudor C. , Vrathasha V. , Chavali Venkata Ramana Murthy , Oliveira-Valença Viviane M. , Tai Wai Lydia , Batchelor Wyndham M. , Yang Xian-Jie , Park Yong , Pan Yuan , Baranov Petr , Di Polo Adriana , Fortune Brad , Gokoffski Kimberly K. , Goldberg Jeffrey L. , Guido William , Kolodkin Alex L. , Mason Carol A. , Ou Yvonne , Reh Thomas A. , Ross Ahmara G. , Samuels Brian C. , Welsbie Derek , Zack Donald J. , Johnson Thomas V. 
Published: September 2023

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.