Multipotential stem cells and progenitors in the vertebrate retina

The vertebrate retina is derived from paired evaginations from the neural tube in embryonic development and is initially produced by progenitor cells similar to those that generate the neurons and glia of other areas of the central nervous system. In some amphibians and fish, the retina continues to grow along with the eye throughout the life of the animal. The new retinal cells are added at the ciliary margin of the eye from the mitotic activity of neural/glial stem cells in a region known as the germinal zone and are seamlessly incorporated into the existing retinal circuitry. Little is known about the cell or molecular biology of these stem cells; however, studies of retinal progenitor cells in chick and mammalian embryos have led to the identification of several factors that control their proliferation. Moreover, studies of retinal regeneration have shown that retinal stem cells can also be derived from two or perhaps three additional sources after retinal damage: (a) the retinal pigmented epithelium (RPE) in amphibians and embryonic chicks and mammals; (b) a specialized rod progenitor in fish; and (c) the Müller glial cells. While there is currently no evidence for a neural/glial stem cell in the adult mammalian retina, and the retina of the mature mammal does not show regenerative capacity after damage, there is a possibility for the reinitiation of stem cell potential at the peripheral retinal margin, from the RPE or from the Müller glial cells. The application of information derived from the studies of retinal progenitor cells in developing organisms should soon provide a test of these possibilities.