Angiogenesis inhibition and choroidal neovascularization suppression by sustained delivery of an integrin antagonist, EMD478761

PURPOSE. To evaluate the angiogenic inhibitory effects of an alpha(v)beta(3)/alpha(v)beta(5) integrin antagonist, EMD478761, released from a polymeric implant in a chick chorioallantoic membrane ( CAM) assay and laser- induced experimental choroidal neovascularization ( CNV) in rats. METHODS. Polyvinyl alcohol- based reservoir implants releasing EMD478761 were designed for placement onto a CAM or intravitreally in rats. In vitro release rates of the implants were measured using HPLC. Angiogenesis was induced on 10- day-old chick embryos by basic fibroblast growth factor ( bFGF), and areas of neovascularization were measured. Experimental CNV was induced in the Brown- Norway rat with a diode laser. EMD478761 or sham microimplants were placed within the vitreous chamber of Brown- Norway rats. Two weeks later, areas of CNV were determined by FITC- dextran staining of choroidal flatmounts. RESULTS. Sustained delivery of EMD478761 significantly inhibited bFGF- induced angiogenesis in CAM, as determined by a reduction in angiogenesis areas, without drug toxicity to the normal CAM vasculature. In an experimental rat model, intravitreal EMD478761 implants significantly suppressed laser- induced CNV compared with intravitreal sham implants, with the mean area reduced by 63% ( P < 0.05). CONCLUSIONS. Sustained delivery of EMD478761demonstrates potent antiangiogenic properties in vivo. These results suggest that an EMD478761 implant may be beneficial in the treatment of neovascular ocular diseases.