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M.N. Cobbs, J.H. Goldman, D.A. Rewolinski; Inhibition of Retinal Blood Barrier Breakdown by VEGFR/PDGFR Inhibitor AG–013958 . Invest. Ophthalmol. Vis. Sci. 2005;46(13):459.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:To evaluate inhibition of VEGF induced leakage by AG–013958, a potent inhibitor of the kinase domain of both VEGFR and PDGFR, in the rat Ocular Miles assay. Methods:Female Adult Spauge–Dawley rats weighing ∼ 200 grams were used for assessment. Rats received intra–vitreal injection of either vehicle, VEGF + vehicle, or VEGF + AG–013958 in the right or the left eye. 24 hours later rats were injected with 45mg/kg Evan’s Blue through a jugular vein catheter and then perfused with 0.2M sodium citrate 1% paraformaldehyde buffer. Blood was drawn from the rats before perfusion to allow the determination of plasma levels of Evan’s Blue in the circulation for normalization between animals. Retinas were dissected and dried in a speed–vac for 5 hours. Evan’s blue was then extracted from the retina with formaldehyde for 18 hours. The resulting amount of Evan’s Blue was then quantified on a Spectra Max plate reader and compared to a standard curve of Evan’s Blue in formaldehyde. Results: AG–013958 dosed in combination with VEGF by intra–vitreal injection inhibited VEGF induced leakage of Evan’s Blue in the rat retina by 94.4% when compared to vehicle. Conclusions: VEGF induces retinal leakage in the rat eye as determined by the Ocular Miles Assay. AG–013958 is a highly effective inhibitor of VEGF induced leakage.
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