Abstract
Abstract: :
Purpose: Anecortave acetate is an angiostatic cortisene devoid of typical glucocorticoid activity that is undergoing phase III trials for the treatment of exudative AMD. Preclinically, anecortave acetate has been shown to reproducibly inhibit angiogenesis elicited by numerous stimuli in a variety of models, including preretinal neovascularization (NV). The following study assessed the utility of anecortave acetate in a commonly used posterior segment model, the mouse model of laser–induced choroidal NV. Method: Choroidal NV (CNV) was induced in C57BL/J mice by rupturing Bruch’s membrane via focal laser photocoagulation. Each mouse received 3–4 laser burns per eye and was randomly assigned as noninjected controls, sham–injected controls, vehicle–injected eyes, or one of three anecortave acetate –injected groups. Control mice received laser OU, where one eye received a sham injection. For intravitreal–injected mice, one laser–treated eye received a 5ul intravitreal injection of 0%, 0.1%, 1%, or 10% anecortave acetate. The pars plana intravitreal injection was performed immediately after laser photocoagulation. Fourteen days post–laser, all mice were euthanized and systemically perfused with fluorescein–labeled dextran. Eyes were then harvested and prepared as choroidal flat mounts, and CNV was quantified with computerized digital analysis. Mean CNV area per mouse was used for comparisons between treatment groups, where P<0.05 was considered significant. Results: An overall significant difference between treatment groups was established (Kruskal Wallis one–way ANOVA, P <0.001). Intravitreal injection of 10% anecortave acetate significantly prevented CNV development by 57.8% as compared to vehicle–injected eyes (Mann–Whitney Rank Sum test, P<0.001). No significant inhibition was observed in eyes treated with 0.1% or 1% anecortave acetate as compared to vehicle. Conclusions: Anecortave acetate provides significant inhibition of laser–induced choroidal neovascularization (CNV) when delivered locally in the adult mouse. These results support the robust package of preclinical efficacy pharmacology for anecortave acetate, thus, further substantiating its potential utility for treating pathologic ocular angiogenesis in man.
Keywords: choroid: neovascularization • pharmacology • age–related macular degeneration