M. Wills

Effect of a novel octapeptide urokinase fragment, A°6, on experimental choroidal neovascularization in the monkey

Purpose: To evaluate the inhibitory effects of a urokinase-derived octapeptide, A˚6, on laser-induced choroidal neovascularization (CNV) in monkeys. Methods: Twenty female cynomolgus monkeys were randomly grouped into weekly or monthly A˚6 treatment groups, each consisting of 10 animals. CNV was induced in both eyes by perimacular laser treatment. In each right eye, a single 22.25-mg A˚6 dose (monthly group) or 4 22.25-mg A˚6 doses each week (weekly group) were given by intravitreal injections. Each left eye received phosphate buffer on the same schedule. Monkeys were observed for 4 weeks by ophthalmic examinations, color photography, and fluorescein angiography. Results: Weekly treated eyes had a 35% reduction of CNV compared with controls (P = 0.23). In contrast, monthly treated eye had a 71% reduction of CNV compared with controls (P = 0.0009). There was no evidence of toxicity at both clinical and pathologic examinations. Conclusions: Intravitreal A˚6 injections effectively inhibited CNV in cynomolgus monkeys without evidence of toxicity. The overall reduction in CNV was greater for monthly treated eyes than for weekly treated eyes. This study suggests that A˚6 has promise as a local antiangiogenic treatment of CNV. Further work is indicated to evaluate the potential role of A˚6 in therapy for human CNV associated with age-related macular degeneration.