Retinal Ganglion Cell Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration
RGC replacement poses a significant challenge because of the inherent complexity of this neuronal class. Prior work supports the premise that RGC replacement is feasible, as individual milestones in RGC replacement have been attained (Figure 1), including RGC differentiation from stem cells, retinal integration of transplanted RGCs, axonal extension through the optic nerve and into the brain, and RGC axon (re)myelination. However, collaborative efforts among interdisciplinary teams are required to brainstorm new ideas, develop rigorous approaches to execute them, and build teams to bring these ideas to fruition, in order to achieve complete RGC pathway replacement. The National Eye Institute (NIH) has prioritized retinal neuronal replacement as part of its strategic goals and is supporting this challenge through the Audacious Goals Initiative (AGI), which promotes collaborative approaches to retinal regeneration that are necessary given the complexity of this task.
RReSTORe aims to exist to complement other collaboratives efforts. RReSTORe will prioritize inclusion of scientists from diverse backgrounds, especially trainees and early career scientists, and adopt a structure that maximizes collaborative and sustained virtual and in-person discussions to foster interpersonal engagement and innovative approaches to RGC regeneration. Our discussions and our work will focus on five major topics:
1) RGC Development and Differentiation: Stem Cell Biology and Neurogenesis; Transdifferentiation; Organoids and Assembloids; RGC subtype identification and specification
2) Transplantation Methods and Models: Transplantation Techniques; In Vivo Imaging and Functional Assays; Large Animal Models of Optic Neuropathy; Transplant Immunology
3) RGC Survival, Maturation, and Host Interactions: Neuroprotection, Neurovascular Coupling; Macroglial Interactions; Microglial Interactions
4) Inner Retinal Wiring: RGC Migration, Tiling, and Patterning; RGC dendritogenesis and Inner Plexiform Layer Sublaminar Targeting; Synaptogenesis in the Inner Plexiform Layer; Functional Integration Assays
5) Eye-to-Brain Connectivity: Pathfinding, Targeting, and Projection Specificity; Synaptogenesis in the Brain; Myelination; Implications of Anterograde Transsynaptic Degeneration