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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.

Recent advancements in electronic materials and subsequent surface modifications have facilitated real-time measurements of cellular processes far beyond traditional passive recordings of neurons and muscle cells. Specifically, the functionalization of conductive materials with ligand-binding aptamers has permitted the utilization of traditional electronic materials for bioelectronic sensing. Further, microfabrication techniques have better allowed microfluidic devices to recapitulate the physiological and pathological conditions of complex tissues and organs in vitro or microphysiological systems (MPS). The convergence of these models with advances in biological/biomedical microelectromechanical systems (BioMEMS) instrumentation has rapidly bolstered a wide array of bioelectronic platforms for real-time cellular analytics. In this review, we provide an overview of the sensing techniques that are relevant to MPS development and highlight the different organ systems to integrate instrumentation for measurement and manipulation of cellular function. Special attention is given to how instrumented MPS can disrupt the drug development and fundamental mechanistic discovery processes. : Biotechnology; Bioelectronics; Bioengineering Subject Areas: Biotechnology, Bioelectronics, Bioengineering