Antagonists of integrin α(v)β₃ inhibit retinal neovascularization in a murine model

Integrin α(v)β₃ is differentially expressed in angiogenic blood vessels in skin granulation tissue, and α(v)β₃ antagonists inhibit angiogenesis in chick chorioallantoic membranes. In this study, we investigated the role of α(v)β₃ in retinal neovascularization. There was no detectable signal for α(v)β₃ by immunohistochemistry in normal human retina, but neovascular tissue removed from the surface of the retina of patients with diabetic retinopathy showed intense staining for α(v)β₃ within the endothelial cells of new blood vessels. In a murine model of oxygen-induced ischemic retinopathy, there was intense staining for α(v)β₃ in endothelial cells participating in neovascularization but no detectable staining in normal retinal blood vessels of adult mice. Synthetic peptides that bind α(v)β₃ and perturb α(v)β₃-mediated adhesion in vitro inhibited retinal neovascularization in the murine model when given by intraperitoneal or periocular injections. These data suggest that α(v)β₃ antagonists may provide a useful adjunct for the treatment of retinal neovascularization.