Regulation of Angiogenesis in CNV by the Akt/Forkhead

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population in the United States. The major reason for severe visual loss in AMD is choroidal neovascularization (CNV), or the formation of abnormal new blood vessels underneath the retina. The goal of this project is to pursue a new direction in CNV research by investigating the role of an intracellular signaling pathway that may play a critical role in the formation of CNV. Our project will be focused on the Akt pathway, which is thought to play a critical role in angiogenesis and appears to be particularly important for endothelial cell survival; therefore inhibition of this pathway may be a clinical strategy for causing regression of existing CNV. It is our overall hypothesis that the Akt signaling pathway plays a major role in mediating the effects of pro- and anti-angiogenic factors (including VEGF and PEDF) in regulating CNV. The specific research in this application is intended to investigate/demonstrate the importance of the Akt signaling pathway in CNV, in order to identify a new therapeutic target. This research will investigate the importance of the Akt pathway in choroidal endothelial cell survival (using cultured choroidal endothelial cells) as well as in a mouse model of CNV. The long-term goal of this research is to gain an enhanced understanding of CNV and provide new molecular targets for the pharmacologic treatment of AMD.