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M. Luke, C. Luke, Tuebingen Bevacizumab Study Group; The Effects of Bevacizumab (Avastin, Genentech) on the Isolated Superfused Vertebrate Retina . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3081.
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For the humanized monoclonal antibody Bevacizumab (AvastinTM, Genentech) targeting vascular endothelial growth factor (VEGF) was shown in vitro to inhibit VEGF–induced cell proliferation, survival, migration and tissue factor production. Abnormal angiogenesis involving VEGF is a central event of the development of choroidal neovascularizations (CNV) in age–related macular degeneration. The present study was designed to evaluate the short–term toxic effects of bevacizumab on retinal function for a therapeutic intraocular application.
The isolated retina technique of bovine retina preparations was used. Bovine retinas were isolated and perfused with an oxygen preincubated nutrient solution. The electroretinogram (ERG) was recorded as a transretinal potential using Ag/AgCl electrodes. After recording of stable ERG–amplitudes, bevacizumab was added in different concentrations to the nutrient solution for 45 min. Thereafter, the retina was reperfused for another 60 min.. The percentage of a– and b–wave reduction during the application of bevacizumab was calculated.
Stable ERG–amplitudes were recorded for more than six hours. During the application of three different concentrations of bevacizumab (0.08 mg/ml, 0.25 mg/ml, 0.8 mg/ml) no significant reduction of the b–wave amplitude was observed. At the same concentrations of bevacizumab no effects on the a–wave amplitudes of the ERG were detected. During the wash out, the b–wave amplitudes as well as the a–wave amplitudes kept constant.
The present study suggests that an intraocular application of 0.25mg/ml bevacizumab for the treatment of choroidal neovascularization in age–related macular degeneration seems possible. Our experimental setup is designed to evaluate short–term effects on retinal function. Long–term effects of bevacizumab at this concentration are improbablely, but cannot be excluded.
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