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S. Luthra, R. Narayanan, L.E. A. Marques, M. Chwa, D.W. Kim, J. Dong, G.M. Seigel, D. Brown, M.C. Kenney, B.D. Kuppermann; Evaluation of in–vitro Safety of Bevacizumab (AVASTINTM) on Retinal Pigment Epithelial and Neurosensory Retinal Cells . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5222.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the in–vitro safety of bevacizumab on human retinal pigment epithelial (ARPE 19) cells and rat neurosensory retinal (R 28) cells.
Cells grown in tissue culture were treated with four concentrations of bevacizumab (AVASTINTM – Genentech, Inc. San Francisco, CA): 0.125mg/ml, 0.25mg/ml, 0.50mg/ml and 1mg/ml. Cell viability was measured after 2, 6 and 24 hours using the trypan blue dye exclusion assay (Beckman Coulter Inc., Fullerton, CA). Statistical analysis was done by ANOVA using GraphPad PrismTM 3.0 version (Graphpad Software Inc., San Diego, CA).
The mean cell viabilities of ARPE 19 cells, after 24 hours exposure to bevacizumab concentrations of 0.125, 0.25, 0.50 and 1mg/ml were 94.3 ± 0.9 %, 95.6 ± 0.9 %, 95.7 ± 0.6 % and 95.1 ± 0.5 % respectively. Untreated ARPE 19 cells (controls) had a mean cell viability of 95.3 ± 1.2%. The mean cell viabilities of R 28 cells, after 24 hours exposure to bevacizumab concentrations of 0.125, 0.25, 0.50 and 1mg/ml were 88.7 ± 1.9 %, 88.4 ± 2.7 %, 86.0 ± 3.9 % and 87.3 ± 2.9 % respectively. Untreated R 28 cells (controls) had a mean cell viability of 89.9 ± 2.4 %. Also, mean cell viabilities of cells at 2 and 6 hours were not significantly different than that of untreated controls (p>0.05).
This study suggests that bevacizumab at concentrations of 0.125mg/ml, 0.25mg/ml, 0.50mg/ml and 1mg/ml (at or above the dose normally used in clinical practice, which is 0.25 – 0.31mg/ml) is safe for human retinal pigment epithelial cells and rat neurosensory retinal cells in–vitro. Vascular endothelial growth factor (VEGF) has been implicated in pathologic neovascularization seen in age–related macular degeneration (AMD), diabetic retinopathy, vein occlusions and neovascular glaucoma. Recently, off–label use of intravitreal bevacizumab (a full–length, humanized, monoclonal antibody against VEGF) has become widespread. Currently, there are no reports in ophthalmic literature of in–vitro safety studies of bevacizumab.
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