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

Loss of retinal ganglion cells (RGCs) in glaucoma and other optic neuropathies leads to irreversible vision loss due to the limited regenerative capacity of the mammalian central nervous system. RGC repopulation—via stem cell–derived neuron transplantation or induction of endogenous transdifferentiation—offers a potential strategy to restore visual function if new neurons can integrate into retinal and central visual circuits. The RGC Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) Consortium was formed to address key barriers to therapeutic repair of the visual pathway. Since 2022, the Consortium has convened international, multidisciplinary discussions to identify five priority areas: (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. This perspective outlines pressing scientific questions, experimental strategies, and cross-disciplinary approaches—from developmental neuroscience and stem cell biology to immunology, biomedical engineering, and regenerative neuroscience—needed to advance RGC repopulation toward clinical translation. The RReSTORe roadmap provides a unified framework for overcoming remaining challenges and achieving transformative therapies for vision restoration in optic neuropathies.