Topical application of integrin antagonists inhibits proliferative retinopathy

The expression of alpha (v)-integrins is highly selective for angiogenic en dothelial cells; ligation inhibition by cyclic RGD peptides prevents pathol ogical neovascularization in tumor or retinopathy models to a large extent. We have previously demonstrated that proliferative retinopathy in a mouse model of retinopathy of prematurity (ROP model) can be reduced by more than 70%. To minimize systemic side effects and unwanted interference with resp onsive angiogenesis, we investigated topical application of cyclic RGD-pept ides. In preliminary experiments, we could exclude any inhibiting effects o f the carrier solution containing EDTA, Na,S, mannitol, hydroxyethyl starch , and benzalconium chloride on the inhibitory effect of cyclic RGD peptides . Retinal presence of small molecular-mass integrin antagonists after topic al application was confirmed using fluorescein-labeled cyclic RGD peptide. Topical application of the peptide to the eye inhibited proliferative retin opathy in a dose-dependent fashion with a maximum of almost 50 %. These res ults suggest that small molecular-mass peptide antagonists of alpha (v)-typ e integrins are efficient in inhibiting proliferative retinopathy by topica l application.