Blindness whether caused by disease, injury, or a developmental defect is a devastating medical problem. to be able to optimize the therapeutic outcome, it is essential to be able to isolate and to study the individual molecules that play a role in the development and repair of the retina and in the formation of appropriate connections between the retina and the visual areas of the brain. We have purified from the retina one of the molecules that may play an important role in these processes and have shown that it is acidic fibroblast growth factor Acidic FGF shares a number of biological and biochemical characteristics with several other peptides including basis FGF, and it is becoming clear that members of the FGF family regulate the survival and differentiation of several classes of nerves from both the PNS and the CNS. A role for FGF in neural regeneration is further indicated by the recent finding of elevated levels of FGF at sites of focal brain injury aFGF stimulates neurite formation by retinal ganglion cells and the expression of opsin by photoreceptor cells, but the full range of FGF action in the neural retina has not yet been defined. The objective of this grant is to explore the potential range of FGF actions in the retina by determining: which cells make FGFs, where the FGFs are stored, and what classes of cells have receptors for the FGFs. We will also determine the effect of injury on the synthesis of FGFs and the expression of FGF receptors. Finally, e will ask whether exogenous FGF can stimulate regeneration by the optic nerve. The long term goal of this project is to continue to use biochemical and molecular techniques to elucidate the role of the FGF in retinal development, to examine the regenerative capacity of the visual system and to determine how regeneration might be influenced by the actions of the FGFs.
| Damon, D H; D'Amore, P A; Wagner, J A (1990) Nerve growth factor and fibroblast growth factor regulate neurite outgrowth and gene expression in PC12 cells via both protein kinase C- and cAMP-independent mechanisms. J Cell Biol 110:1333-9 |
| Damon, D H; Lobb, R R; D'Amore, P A et al. (1989) Heparin potentiates the action of acidic fibroblast growth factor by prolonging its biological half-life. J Cell Physiol 138:221-6 |
| Damon, D H; D'Amore, P A; Wagner, J A (1988) Sulfated glycosaminoglycans modify growth factor-induced neurite outgrowth in PC12 cells. J Cell Physiol 135:293-300 |
| Wagner, J A; D'Amore, P A (1986) Neurite outgrowth induced by an endothelial cell mitogen isolated from retina. J Cell Biol 103:1363-7 |
