The discovery and study of adult stem cells have revolutionized regenerative medicine by offering new opportunities for treating various medical conditions. Anamniote stem cells, which retain their full proliferative capacity and full differentiation range throughout their lifetime, harbour a greater potential compared to mammalian adult stem cells, which only exhibit limited stem cell potential. Therefore, understanding the mechanisms underlying these differences is of significant interest. In this review, we examine the similarities and differences of adult retinal stem cells in anamniotes and mammals, from their embryonic stages in the optic vesicle to their residence in the postembryonic retinal stem cell niche, the ciliary marginal zone located in the retinal periphery. In anamniotes, developing precursors of retinal stem cells are exposed to various environmental cues during their migration in the complex morphogenetic remodelling of the optic vesicle to the optic cup. In contrast, their mammalian counterparts in the retinal periphery are primarily instructed by neighbouring tissues once they are in place. We explore the distinct modes of optic cup morphogenesis in mammals and teleost fish and highlight molecular mechanisms governing morphogenesis and stem cells instruction. The review concludes with the molecular mechanisms of ciliary marginal zone formation and offers a perspective on the impact of comparative single cell transcriptomic studies to reveal the evolutionary similarities and differences.

Rare retinal stem cells (RSCs) within the ciliary epithelium at the retinal margin of the adult mouse and human eyes can divide in vitro in the absence of growth factors to generate clonal, self-renewing spheres which can generate all the retinal cell types. Since no regenerative properties are seen in situ in the adult mammalian eye, we sought to determine the factors that are involved in the repression of endogenous RSCs. We discovered that factors secreted by the adult lens and cornea block the proliferation of adult RSCs in vitro. Bone morphogenetic protein (BMP)2, BMP4, and secreted frizzled related protein 2 were identified as principal effectors of the anti-proliferative effects on RSCs. As a similar induced quiescence was observed in vitro on both mouse and human RSCs, targeting these molecules in vivo may reactivate RSCs directly in situ in the eyes of the blind.