Age-related macular degeneration: signal transduction leading to changed secretion of angiogenic factors by retinal pigment epithelial cells from excised neovascular membranes

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The aim of this study is to gain new insights into angiogenesis-inducing mechanisms in age-related macular degeneration. Secretion of angiogenic factors by the retinal pigment epithelium (RPE) plays a central role in this process. This secretion is auto-/paracrine-stimulated or induced by changes in the microenvironment of these cells. Cellular physiological studies using patch-clamp techniques will be performed on freshly isolated or cultured RPE cells from proliferative or neovascular membranes obtained by eye surgery in patients with age-related macular degeneration. The characteristics of mainly Ca2+ and K+ channels expressed in these RPE cells will be investigated in order to study their differentiation. Then the intracellular signal transduction of secretion-stimulating factors will be described. Studies on signal transduction will be focused on stimulation by growth factors, advanced glycation endproducts and integrin ligands. Adding lucifer yellow to the pipette solution for whole-cell recordings on freshly isolated RPE cells allows the subsequent immunohistochemical analysis for identification. For purposes of comparison, the signal transduction of secretion-stimulating factors in cultured human and rat RPE cells will be studied by patch-clamp techniques and biochemical methods.