γ-Secretase Regulates VEGFR-1 Signalling in Vascular Endothelium and RPE

In conclusion, gamma-secretase is expressed in both retinal microvascular endothelial cells and RPE cells and is able to elicit regulated intramembrane proteolysis of VEGFR1. Furthermore, gamma-secretase regulates the translocation of the intracellular domain of VEGFR1 as well as full length VEGFR1 in both cell types. Gamma-secretase is clearly able to act as a potent negative regulators of VEGFR2 induced in vitro angiogenesis but its role in the RPE has yet to be elucidated. We conclude that gamma-secretase may offer a therapeutic target for the treatment of both retinal and choroidal neovascularization.