Pathways Regulating Angiogenesis in Epithelial Cells

Bruch’s membrane is a layer of retinal tissue upon which the retinal pigment epithelium (RPE) lies. Just below Bruch’s membrane is the choroid layer, a region containing many blood vessels and capillaries. The increased growth of new capillaries in the choroid layer (as seen in wet macular degeneration) is initiated through the action of growth factors on endothelial cells, which are the building blocks of capillaries. Vascular endothelial growth factor (VEGF) has been identified as the principal agent responsible for new capillary growth (angiogenesis) in the body. However, it is also known that other growth factors can participate in the progression of ocular neovascularization. These factors have been identified as bFGF, TGFß, PDGF, and IGF-1. So far, there is little information on the role that IGF-1 plays in neovascularization, but Dr. Rosenzweig has shown that IGF-1 stimulates the secretion of VEGF by RPE cells in culture. He is now studying how VEGF secretion is regulated in human RPE cells in tissue culture by treating them with IGF-1 or hypoxic conditions. This study could lead to the identification of new drug targets for the inhibition of choroidal neovascularization in age-related macular degeneration.