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J Cao, R Renard, Q Wang, GD Yancopoulos, SJ Wiegand; Inhibition of Corneal Neovascularization and Inflammation by VEGF Trap . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1863.
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Purpose: To determine the efficacy of a new angiogenesis inhibitor VEGF Trap on the development of corneal neovascularization. Systemic administration of the VEGF Trap (a fusion protein comprising the ligand binding domains of VEGF receptors and Human Fc) was investigated in two mouse models of corneal injury. Methods: Corneal neovascularization was induced by intrastromal placement of 3 nylon sutures, or by chemical injury and mechanical debridement of the corneal epithelium in male C57BL mouse. The VEGF Trap (25mg/kg body weight) was administered systemically, once or at multiple time points before or following injury. The growth of corneal neovessels was evaluated on days 4, 7, 9 and 16 by slit-lamp microscopy and histologically. The vasculature was labeled with an endothelial specific fluorescein conjugated lectin (lycopersicon esculentum), and neovascularization was evaluated in corneal flat-mount, as well as in cross sections using PECAM immunohistochemistry. Corneal edema also was evaluated with slit lamp microscopy and corneal thickness was evaluated in cross-sections. The numbers of polymorphonucleocytes (PMN) and macrophages were determined by staining cross-sections with HEMA-3 or rat anti-mouse F4/80 monoclonal antibody, respectively. The Scion Image program was used for analysis of the area and length of corneal neovessels. Results: VEGF Trap treatment significantly inhibited corneal neovascularization in all dosing regimens tested, in both suture (P< 0.001) and chemical injury (P< 0.001) models. When treatment was begun within 5 days of injury, corneal neovascularization was completely blocked. Corneal edema also was significantly reduced in VEGF Trap treated animals compare to vehicle treated controls, and histological studies showed that the infiltration of PMNs and macrophages into the damaged cornea was also dramatically reduced with VEGF Trap treatment. Conclusion: VEGF Trap inhibited the development of corneal neovascularization, effectively prevented edema, and markedly reduced the infiltration of leukocytes and macrophages in both corneal injury models. These results indicate that VEGF Trap is a potent inhibitor of pathologic angiogenesis, with potential therapeutic applications in the treatment of corneal neovascularization. CR: E
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