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(Investigative Ophthalmology and Visual Science. 2007;48:5184-5190.)
© 2007 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.07-0469
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Angiogenesis Inhibition and Choroidal Neovascularization Suppression by Sustained Delivery of an Integrin Antagonist, EMD478761

Yingli Fu,1,2 M. Lourdes Ponce,1 Michelle Thill,1 Peng Yuan,3 Nam Sun Wang,2 and Karl G. Csaky1

1From the National Eye Institute and the 3Pharmacy Department, Clinical Center, National Institutes of Health, Bethesda, Maryland; and the 2Fischell Department of Bioengineering, University of Maryland, College Park, Maryland.

PURPOSE. To evaluate the angiogenic inhibitory effects of an {alpha}vß3/{alpha}vß5 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.




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