Understanding retinal regeneration: Core mechanisms and biological insights

Retinal regeneration is a complex, evolutionarily constrained process, resulting in the restoration of retinal structure and function upon injury. This capacity varies widely across species. In this review, we highlight current knowledge on the cellular and molecular basis of retinal regeneration and ask why regenerative capacity is maintained in some lineages but lost in others. We first situate regeneration within an evolutionary framework, contrasting regenerationcompetent with regeneration-deficient species. We then examine two principal cellular sources of retinal regeneration, which are the Müller glia and the retinal pigment epithelium, focusing on their physiological roles, injury responses and the gene-regulatory networks that govern regenerative potential. We review experimental approaches to induce retinal regeneration in mammals as a future treatment strategy for human retinal disease and discuss key obstacles. Finally, we outline future directions, emphasizing how integrating knowledge of intercellular signaling, immune modulation, and tissue plasticity can guide efforts to unlock regenerative pathways in the human retina.