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Q Wang, R Renard, J Cao, D Yancopouls, SJ Wiegand; Anti-Angiogenic Properties of a New VEGF Antagonist, VEGF Trap, in a Mouse Model of Retinal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3714.
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Purpose: Excessive upregulation of VEGF expression appears to be responsible for pathologic neovascularization in many retinal diseases. We have developed a new VEGF antagonist, VEGF Trap, that binds VEGF with high affinity thereby neutralizing its action. The current study investigates the anti-angiogenic properties of VEGF Trap in a mouse model of oxygen-induced retinopathy (OIR). Method: OIR mice were produced following the method developed by Smith et al (IOVS 1994, 35:101-111). VEGF Trap (25mg/kg body weight) was administered by intraperitoneal (ip) injection every other day from PN13 (12-24 hours after returning the mice from hyperoxia to room air) to PN17. Littermates exposed to the same regimen of hyperoxia, received ip injections of 50 µl of PBS upon to room air and served as controls. Eyes were taken on PN19, and one retina was flat mounted and stained with fluorescent Griffonia simplicifolia lectin B4 to visualize the retinal vasculature. The contralateral eye was embedded, sectioned and stained with hematoxylin and eosin. Results: One week following return to room air (PN19), the retinas of all control mice exposed to hyperoxia exhibited marked pathologic angiogenesis, characterized by the presence of vascular tufts penetrating the inner limiting membrane and chaotic sprouting of vessels on the surface of the retina. Administration of VEGF Trap almost completely blocked the development of these vascular abnormalities. Although pathologic angiogenesis was dramatically inhibited, administration of the VEGF trap did not block all retinal angiogenesis. Remarkably, by PN 19 much of the central retina was appropriately revascularized in animals treated with VEGF Trap, as evidenced by the regrowth of normal appearing vessels in the superficial, intermediate and deep layers. Conclusion: Systemic administration of VEGF Trap can efficiently suppress pathologic retinal angiogenesis without blocking the appropriate revascularization of the previously ischemic retina. This finding distinguishes the anti-angiogenic properties of VEGF Trap from many other angiogenesis inhibitors studied in this model, which appear to be either substantially less effective in blocking pathologic angiogenesis (Aiello LP et al. PNAS 1995, 92:10457-10461), or which also compromise the appropriate revascularization of the retina (Ozaki et al. Am J Pathol 1997, 156:697-707).
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