Effect of a novel octapeptide urokinase fragment, Å6, on experimental choroidal neovascularization in the monkey

Abstract

Abstract: : Purpose:To evaluate the inhibitory effects of a urokinase–derived octapeptide, Å6, on laser–induced choroidal neovascularization (CNV) in monkeys. Methods: Twenty female cynomolgus monkeys were randomly grouped into weekly and monthly Å6 treatment group, each consisting of 10 animals. CNV was induced by peripheral macular laser treatment to both eyes. In each right eye, intravitreal injections of Å6, 22.25 mg per eye, were given, while each left eye received phosphate buffer. Monkeys were observed for 4 weeks by ophthalmic examinations, color photographs, and fluorescein angiography. Results:Angiography showed an average of 35 % reduction of CNV in the weekly treated eyes, compared to control (P= 0.23). Monthly treated eyes showed 71 % reduction of CNV, compared to controls (P=0.0009). There was no evidence of toxicity on both clinical and pathologic examination. Conclusions:Intravitreal Å6 injections effectively inhibited CNV in cynomolgus monkeys. The reduction in CNV was as high as 76% without evidence of toxicity. This study suggests that Å6 has promise as a local anti–angiogenic treatment of CNV. Further work upon Å6 is indicated to evaluate its potential role in the therapy of human CNV.

Keywords: choroid: neovascularization • age–related macular degeneration • pharmacology