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J. Cao, Y. Liu, W. Xiao, R. Wen, G. D. Yancopoulos, S. J. Wiegand; VEGF Trap Promotes Regression of Choroidal Neovascularization (CNV) and Inhibits Fibrosis and Inflammation in the Subretinal Matrigel CNV Model. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2979.
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Subretinal deposition of matrigel induces CNV in rodents, reminiscent of the lesions seen in the ‘wet’ form of age-related macular degeneration (Wen, et al. IOVS 2002 43: E-abstract 1297). The present study evaluates the effects of systemic VEGF Trap on the development and progression of CNV, as well as associated fibrosis and inflammation in the subretinal Matrigel model of CNV.
CNV was induced in adult male Sprague-Dawley rats by subretinal injection of a 75% matrigel solution (1.2 µl). Ten days later, the extent of CNV was evaluated in one group of rats. The remaining animals received injections of a VEGF Trap (12.5mg/kg, SC) or a control protein (human Fc, 10mg/kg, SC) on days 10, 13 and 16. On day 20 the vasculature was labeled by perfusion of a DiI solution, the eyes harvested and serial sections (50 µm) cut on a cryostat through the area of the matrigel deposit, and examined by fluorescence microscopy. The lesion and CNV areas were measured in every third section, and the total CNV and lesion volumes were calculated. Alternate series of sections were stained with hematoxylin or Masson’s Trichrome stain, or with antibodies against CD45 or Vimentin to characterize leukocyte infiltration and fibrosis in the Matrigel injected area.
Neovessels originating from the choroid were present in the matrigel deposit and adjacent subretinal space 10 days after injection. On day 20, the CNV blood vessel volume in animals treated with VEGF Trap was 16.6% of CNV volume in untreated rats on day 10, representing an 83.4% reduction from the 10-day baseline. In contrast, the CNV vessel volume was 65.4% greater in Fc controls at day 20 than in untreated animals at day10. In addition, subretinal fibrosis and leukocyte infiltration were markedly reduced in eyes in the VEGF Trap treatment group, as compared with the Fc controls. The total lesion volume was reduced by 73.2% in the treated group, compared with Fc controls.
These findings demonstrate that VEGF Trap blocked further development of CNV, and more importantly, it promoted the regression of recently formed CNV in rats. In addition, VEGF Trap treatment greatly reduced the associated fibrosis and inflammation, as well as the lesion volume. Our data provide new insight into the pathogenesis and development of CNV.
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