Müller glial cells for regeneration, retinal organoids, cell transplantation, and neuroprotection

Müller glial cells are essential for retinal structure and homeostasis and increasingly recognized as dual regulators of retinal degeneration and regeneration. Beyond providing metabolic and structural support, Müller glial cells actively shape disease progression while retaining latent regenerative potential. Growing evidence highlights their roles in retinal degeneration, development, and neuroprotection, particularly in age-related macular degeneration, diabetic retinopathy, and inherited retinal disorders. This review integrates recent advances across five key areas: (1) Müller glial cell dysfunction in retinal disease pathology, including gliosis, inflammatory signaling, and vascular dysregulation; (2) their regenerative capacity, with a critical appraisal of efforts to reprogram Müller glial cells into retinal progenitors in mammalian models and the ongoing controversy surrounding functional neuronal replacement; (3) their contribution to the maturation of induced pluripotent stem cells-derived retinal organoids; (4) their neuroprotective roles through antioxidant, immunomodulatory, and trophic mechanisms; and (5) their emerging applications in cell-based therapies. By highlighting unresolved knowledge gaps-particularly the molecular barriers limiting Müller glial cell reprogramming and the signals governing their switch between protective and pathogenic states, this review positions Müller glial cells as central targets for future retinal regenerative and therapeutic strategies.