Molecular responses of choroidal endothelial cells to elastin derived peptides through the elastin-binding protein (GLB1)

PurposeNeovascular AMD involves the activation of choroidal endothelial cells to increase their inflammatory and angiogenic behaviors. Elastin derived peptides (EDPs) can elicit some of these phenotypic changes in endothelial cells. This investigation was performed to follow up on those findings by determining a receptor for these peptides in the human eye as well as evaluating the effects of elevated EDPs on choroidal cells in vitro and in vivo.MethodsThe expression of elastin receptor genes including GLB1 was analyzed using reverse transcription PCR. Migration of choroidal endothelial cells was quantified in the presence of inhibitors to different EDP binding proteins. C57BL6 mice were injected with EDPs and studied by electroretinography, transmission electron microscopy, and microarray analysis.ResultsAn alternatively spliced form of beta-galactosidase (GLB1) is present on human choroidal endothelial cells and acts as a receptor for EDPs. Elevated levels of circulating EDPs do not affect retinal function in the mouse, but do increase the expression and deposition of collagen IV in the RPE/choroid complex.ConclusionsEDPs may play a role in neovascular AMD by binding to and inducing neovascular phenotypes in choroidal endothelial cells through their receptor, GLB1. These peptides also cause an increased mRNA expression and deposition of collagen IV in the RPE/choroid, which may alter diffusion properties between the retina and choriocapillaris.

► Abnormal choroidal angiogenesis can occur in age-related macular degeneration.
► Elastin fragments from Bruch's membrane may induce angiogenesis.
► The mechanism of choroidal endothelial cell activation by elastin was explored.
► We found expression of elastin receptor on human choroidal EC.
► Circulating elastin pepides alter ocular gene expression of ECM genes.