SUBCUTANEOUS INJECTION OF A CYCLIC PEPTIDE ANTAGONIST OF VITRONECTIN RECEPTOR-TYPE INTEGRINS INHIBITS RETINAL NEOVASCULARIZATION

Retinal neovascularization is a major cause of blindness in such disor ders as retinopathy of prematurity, proliferative diabetic retinopathy and senile macular degeneration. Because ligation of vitronectin rece ptor-type integrins appears to be required for the survival and matura tion of newly formed but not quiescent blood vessels in several vascul ar beds including the retina, blockade of this downstream adhesion rec eptor system was investigated. In a mouse model of hypoxia-induced ret inal neovascularization twice daily administration of 1 to 20 mg cycli c alpha(nu)-integrin antagonist peptide per kilogram of body weight re duced capillary proliferation in a dose-dependent fashion - maximum 76 % - without obvious side effects. A cyclic control peptide displayed n o inhibitory effect on neovascularization. These findings indicate tha t systemic application of vitronectin receptor antagonists appears to be clinically feasible and is efficient in preventing retinal neovascu larization and superior to cytokine-blocking strategies.