INVOLVEMENT OF INTEGRINS ALPHA(V)BETA(3) AND ALPHA(V)BETA(5) IN OCULAR NEOVASCULAR DISEASES

Angiogenesis underlies the majority of eve diseases that result in cat astrophic loss of vision. Recent evidence has implicated the integrins alpha(v) beta(3) and alpha(v) beta(5) in the angiogenic process. We e xamined the expression of alpha(v) beta(3) and alpha(v) beta(5) in neo vascular ocular tissue from patients with subretinal neovascularizatio n from age-related macular degeneration or the presumed ocular histopl asmosis syndrome or retinal neovascularization from proliferative diab etic retinopathy (PDR). Only alpha(v) beta(3) was observed on blood ve ssels in ocular tissues with active neovascularization from patients w ith age-related macular degeneration or presumed ocular histoplasmosis , whereas both alpha(v) beta(3) and alpha(v) beta(5) were present on v ascular cells in tissues from patients with PDR. Since we observed bot h integrins on vascular cells from tissues of patients with retinal ne ovascularization from PDR, we examined the effects of a systemically a dministered cyclic peptide antagonist of alpha(v) beta(3) and alpha(v) beta(5) on retinal angiogenesis in a murine model. This antagonist sp ecifically blocked nerv blood vessel formation with no effect on estab lished vessels. These results not only reinforce the concept that reti nal and subretinal neovascular diseases are distinct pathological proc esses, but that antagonists of alpha(v) beta(3) and/or alpha(v) beta(5 ) may be effective in treating individuals with blinding eye disease a ssociated with angiogenesis.