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Ivan B. Lobov, Eunice Cheung, Stanley J. Wiegand, George D. Yancopoulos; VEGF Trap Treatment Regresses Pathological Neovessels, Improves Revascularization and Reduces Retinal Ischemia in the Murine Oxygen-Induced Retinopathy (OIR) Model. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3128.
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In the OIR model, hyperoxia induces vaso-obliteration in the central retina of neonatal mice followed by ischemia-driven pathological neovascularization when animals are returned to room air. We have previously reported that systemic and intravitreal administration of VEGF Trap, a potent VEGF inhibitor which binds all VEGF-A isoforms and PlGF, blocks pathological neovascularization in this model (IOVS 2006;47: E-Abstract 1750). The present studies assess the effects of VEGF Trap on established pathological neovessels, retinal revascularization and retinal ischemia/hypoxia.
OIR was produced following the method developed by Smith et al (IOVS, 1994, 35:101-111). To assess the effect VEGF Trap on retinal revascularization, VEGF Trap or a control protein, hFc, was administered on P12, one day following return to room air. At P16 eyes were enucleated, stained with FITC-labeled Griffonia Simplicifolia (GS) lectin I and flat-mounted. Hypoxyprobe was injected P16, eyes were harvested one hour later, and stained with anti-hypoxyprobe FITC-labeled antibody. To study the effects of VEGF Trap on the established neovascularization, hFc or VEGF Trap was injected on P15 and eyes were harvested 24 hours later.
At optimal doses, VEGF Trap treatment was associated with accelerated regrowth of retinal blood vessels. Hypoxyprobe labeling revealed a marked, concomitant reduction in the hypoxic/ischemic areas in VEGF Trap treated retinas. Notably, hypoxyprobe labeling was reduced by VEGF Trap treatment not only in the central retina where capillaries had been lost, but also in the retinal periphery which remained vascularized following exposure to hyperoxia. This indicates that in addition to enhancing regrowth the regrowth of retinal blood vessel, VEGF Trap treatment can also enhance circulation in the immature components of the vasculature in the peripheral retina that survive the initial hypoxic injury. When administered at P15, after the establishment of pathological neovascularization, VEGF Trap induced a rapid and essentially complete regression of the abnormal neovessels within 24 hours of administration.
Administration of VEGF Trap shortly after return to room air not only prevents pathological neovascularization, but can also promote faster regrowth of the normal blood vessels, and improve overall retinal perfusion. When administered after pathological neovascularization is established, VEGF Trap induces the rapid regression of the abnormal vasculature.
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