Topical application of integrin antagonists inhibits proliferative retinopathy

The expression of α_v-integrins is highly selective for anglogenic endothelial cells; ligation inhibition by cyclic RGD peptides prevents pathological 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 responsive angiogenesis, we investigated topical application of cyclic RGD-peptides. In preliminary experiments, we could exclude any inhibiting effects of the carrier solution containing EDTA, Na₂S, mannitol, hydroxyethyl starch, and benzalconium chloride on the inhibitory effect of cyclic RGD peptides. Retinal presence of small molecular-mass integrin antagonists after topical application was confirmed using fluorescein-labeled cyclic RGD peptide. Topical application of the peptide to the eye inhibited proliferative retinopathy in a dose-dependent fashion with a maximum of almost 50%. These results suggest that small molecular-mass peptide antagonists of α_v-type integrins are efficient in inhibiting proliferative retinopathy by topical application.