Retinal stem cells and their ability to regenerate the retina have been well-characterized in cold-blooded vertebrates. Recently, the identification of neural stem cells within the eyes of warm-blooded vertebrates has raised the possibility of retinal regeneration in humans. Dr. Fischer has recently identified a zone of neural progenitors at the retinal margin of the chicken eye that is similar to that found in frogs and fish. He proposes to study the effects of the secreted factor glucagon on the proliferation and differentiation of neural progenitors in the embryonic and postnatal chicken retina. Glucagon is best known as a physiological antagonist to insulin in regulating serum glucose levels. He has previously demonstrated that insulin and IGF-I stimulate the proliferation of progenitors at the retinal margin. Interestingly, preliminary data indicates that the dendrites of glucagon-containing amacrine cells within the retina are heavily clustered in the zone of progenitors at the retinal margin. In addition, preliminary data suggest that glucagon suppresses the proliferation of neural progenitors at the retinal margin in opposition to the effects of insulin; a striking parallel to the opposing roles of these factors in blood-glucose homeostasis. The experiments outlined in this proposal aim to identify the mechanisms by which glucagon regulates the proliferation and differentiation of neural progenitors in the developing embryonic retina and at the retinal margin of the postnatal chicken. These findings would ascribe a new function for glucagon and for the first time implicate glucagon as a secreted factor that regulates the development of the central nervous system. An understanding of the factors and mechanisms that control the proliferation and differentiation of retinal progenitors could provide a basis by which to stimulate retinal regeneration from stem cells. Knowledge gained from studies on retinal stem cells in the chicken could be applied to rational therapies for sight-threatening disorders of the human retina.
