Intravitreal injection of VEGF siRNA inhibits growth and leakage in a non human primate laser induced model of CNV

Abstract

Abstract: : Purpose: To determine the safety and efficacy of siRNA directed against VEGF in a non–human primate model of laser induced choroidal neovascularization (CNV). Methods: Each animal received laser photocoagulation to induce CNV in both eyes. Each animal was then randomized to receive 0.05 ml of either vehicle alone or VEGF siRNA at 70 µg, 150 µg, or 350µg in both eyes by intravitreal injection. Eyes were monitored weekly by ophthalmic examination, color photography and fluorescein angiography for 36 days after laser. Electroretinograms were measured at baseline and at 5 weeks post laser. CNV on fluorescein angiograms were measured for area and graded for clinically significant leakage in a standardized, randomized and double masked fashion on day 15, 22, 29, and 36 post laser. Results: VEGF siRNA did not cause any change in ERG, hemorrhage, inflammation or clinical signs of toxicity. A single administration of VEGF siRNA significantly inhibited growth of choroidal neovascularization and attenuated angiographic leakage in a dose dependent manner. Conclusions: Intravitreal injection of VEGF siRNA is capable of inhibiting the growth and vascular permeability of laser induced choroidal neovascularization in a non–human primate in a dose dependent manner. This study demonstrates pre–clinical proof of principle which supports proceeding to clinical studies of VEGF siRNA in patients with exudative age–related macular degeneration.

Keywords: choroid: neovascularization • pathology: experimental • growth factors/growth factor receptors