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F.E. Wang, G. Shi, M.R. Niesman, D.A. Rewolinski, S.S. Miller; VEGF Receptor Inhibitors (AG13764 and AG13711) Reverse VEGF–Induced Choroidal Neovascularization in Rat Eye . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5305.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Age–related macular degeneration (AMD) is the major cause of blindness for people over 60. In the wet form of AMD, VEGF is a major stimulator of choroidal neovascularization (CNV). Compounds targeting VEGF signaling have been a major focus for developing therapy. We have previously developed a rat model of CNV. We have used this model to examine the ability of AG13764 and AG13711 (Pfizer) to reverse VEGF–induced CNV. Methods: AAV–VEGF was injected into subretinal space of rats at postnatal days 16–18. Six weeks later, suspension of AG13764 and AG13711 were injected intraperitoneally (IP, twice daily) or intravitreally (every five days) over a two week period. FITC–dextran whole–mounts of RPE–choroid–sclera were prepared after the animals were sacrificed. CNV area was quantified using Neurolucida. Data from intravitreal and intraperitoneal injections were analyzed by a Wilcoxon signed rank test and a Mann Whitney test, respectively. Histology and immunohistochemistry were done as previously described (Wang, et al., IOVS, 44: pg 781–790, 2003). Results: VEGF expression was confirmed by immunohistochemistry. In 12 of 13 animals, the level of CNV was reduced by 16% to 100% (p< 0.005, median 75%), following intravitreal injections of AG13764. In 11 of 12 animals, the level of CNV was also reduced by 16% to 100% (p< 0.01, median 56%), following intravitreal injection of AG13711. In three groups of IP injected animals (8–10 eyes per group), AG13764 vs control, the median CNV level was reduced by 48% (p< 0.05) in the treated eye. In AG13711 treated animals, the median area of CNV was reduced by 40% compared to control. Histological sections show recovery of retinal morphology in treated eyes. Conclusions: These data indicate that both compounds reduce blood vessel proliferation in our AAV–VEGF model of CNV, whether they are delivered directly into the eye or systemically. This reduction in CNV area is an underestimate since it does not reflect changes in volume.
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