Gamma-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.
Boulton
Michael E
ME
Ophthalmology and Visual Sciences, University of Texas Medical Branch, Galveston, Texas 77550, USA. boultonm@utmb.edu
Cai
Jun
J
Grant
Maria B
MB
Zhang
Yadan
Y
D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002199:Capillary Permeability / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006868:Hydrolysis; D008024:Ligands; D009389:Neovascularization, Pathologic / Q000473:pathology; D010857:Pigment Epithelium of Eye / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000737:chemistry / Q000378:metabolism*
D008024:Ligands; D020033:Protein Isoforms; D040281:Vascular Endothelial Growth Factor Receptor-1; D053829:Amyloid Precursor Protein Secretases