The major objective of our laboratory is to gain a greater understanding of the cellular and molecular aspects of retinal repair and regeneration, processes that are relevant to proliferative retinopathies, retinal degenerations, subretinal neovascularization, and retinal transplantation.
In addition to several well-characterized functions that are essential for normal retinal functioning, the retinal pigmented epithelium (RPE) plays a central role in retinal repair and provides trophic influences critical for photoreceptor development and maintenance. These aspects of RPE function may provide the basis for RPE participation in proliferative retinopathies, some retinal degenerations, return of function after retinal insults (e.g. retinal detachment, subretinal neovascularization), and for a potential future role in retinal transplantation. Our laboratory is studying the role of peptide growth factors and neurotrophic factors in these processes to identify new avenues for therapeutic intervention. Using in vitro models and animal models of wound repair, we have demonstrated that PDGF plays an important role in growth regulation in the retina and RPE. There is an autocrine loop for PDGF that is upregulted after various type of injury to the retina and RPE. Basic FGF appears to play a critical role in neurotrophic interactions. Photoreceptor-specific expression of dominant-negative FGF receptor mutants results in retinal degeneration suggesting that one or more FGF is a survival factor in photoreceptors. We have demonstrated neurotrophin receptors on RPE cells that when activated increase expression of basic FGF. We are currently using cell specific promoters to overexpress growth factors and neurotrophins to determine their effect normally in the retina and in models of retinal degeneration. In this manner, and by perturbing receptor function with dominant-negative mutations, we hope to identify the role of specific factors in trophic and proliferative interactions in the retina.