Growth factors have been implicated in many important functions in the retina, including development and differentiation, cell survival, and wound repair. They have also been implicated in the pathogenesis of several disease processes including exaggerated wound repair leading to scarring and retinal detachment, ocular neovascularization, and retinal degenerations. In order to modulate the normal and pathologic roles of growth factors, it is important to have a detailed understanding of how alterations in their expression in the retina affect retinal structure and function. In past grant periods, we have demonstrated that the expression of platelet-derived growth factor (PDGF)-A and PDGF-B, and their receptors are increased in vitro and in vivo in models of retinal and retinal pigmented epithelial (RPE) cell wound repair and proliferative retinopathies, while fibroblast growth factor (FGF) signaling is necessary for photoreceptor cell survival. In this grant period, we plan to use tissue- specific promoters in transgenic mice to study the effects of altered expression of each of these factors in the retina. Using photoreceptor- specific promoters (rhodopsin or inter photoreceptor retinol binding protein) or the neuron-specific enolase promoter, which drives expression in the inner retina, we will control the location of expression in the retina. In addition, we will use the tetracycline-induced promoter system to control the timing and duration of expression. We will determine the effect of altered expression of these factors in the retina at various stages of development and in several models of proliferative retinopathies or retinal degenerations. This will provide important new information that is needed for the development of new treatments for these disease processes.
