OLIGODEOXYNUCLEOTIDES INHIBIT RETINAL NEOVASCULARIZATION IN A MURINE MODEL OF PROLIFERATIVE RETINOPATHY

Diseases characterized by retinal neovascularization are among the pri ncipal causes of visual loss worldwide. The hypoxia-stimulated express ion of vascular endothelial growth factor (VEGF) has been implicated i n the proliferation of new blood vessels, We have investigated the use of antisense phosphorothioate oligodeoxynucleotides against murine VE GF to inhibit retinal neovascularization and VEGF synthesis in a murin e model of proliferative retinopathy. Intravitreal injections of two d ifferent antisense phosphorothioate oligodeoxynucleotides prior to the onset of proliferative retinopathy reduced new blood vessel growth a mean of 25 and 31% compared with controls. This inhibition was depende nt on the concentration of antisense phosphorothioate oligodeoxynucleo tides and resulted in a 40-66% reduction in the level of VEGF protein, as determined by Western blot analysis. Control (sense, nonspecific) phosphorothioate oligodeoxynucleotides did not cause a significant red uction in retinal neovascularization or VEGF protein levels. These dat a further establish a fundamental role for VEGF expression in ischemia -induced proliferative retinopathies and a potential therapeutic use f or antisense phosphorothioate oligodeoxynucleotides.