Retinal Stem Cells

Abstract

The vertebrate retina is a well-characterized central nervous system (CNS) structure, consisting of seven major cell types, which in adult are arranged in a stereotypical laminar organization. These cell types are born in an evolutionarily conserved temporal sequence: the majority of retinal ganglion cells (RGCs), horizontal cells, amacrine cells, and cone photoreceptors are born during early histogenesis, whereas the majority of rod photoreceptors, bipolar cells, and the Muller glia are generated during late histogenesis (1). Thus, as elsewhere in the CNS (2), neurogenesis in the retina precedes gliogenesis. Underlying cellular diversity in the retina is population of neural progenitors that generate stage-specific neurons and glia (3). Evidence from a variety of experimental approaches including cell ablation studies and in vivo lineage analyses demonstrated that neural progenitors in the developing retina were multipotential, possessing capacity to generate all seven retinal cell types, including the Muller glia (4, 5, 6, 7, 8). Although retinal progenitors have not been demonstrated to possess the potential of self-renewal (9,10), a hallmark of stem cells, they are included within the broad description of stem cells, with the assumption that they possess the potential of self-renewal. Potentially this is not demonstrable in vitro because of a lack of a conducive environment (3). In mammals and other warm-blooded vertebrates, neural stem cells are found only in the embryonic retina (11, 12, 13). Recently a quiescent population of neural stem cells with retinal potential has been identified in the ciliary epithelium of warm-blooded vertebrates (13, 14, 15). These cells are regarded as analogous to those found in the ciliary marginal zone (CMZ) of adult fish and frog retina (11,16,17). In adult fish, neural stem cells are not confined to CMZ but are also located in the inner retina and are regardedto generate rod photoreceptors during regeneration and in response to injury (16).