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S. Luthra, J. Dong, A. Neekhra, A. L. Gramajo, G. M. Seigel, D. J. Brown, M. C. Kenney, B. D. Kuppermann; Effect of Bevacizumab (AvastinTM) on Mitochondrial Function of Retinal Pigment Epithelial, Neurosensory Retinal and Microvascular Endothelial Cells in Culture. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2197.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the effect of bevacizumab on mitochondrial function of human retinal pigment epithelial cells (ARPE-19), rat neurosensory retinal cells (R28) and human microvascular endothelial cells (HMVECad) in culture.
ARPE-19 and R28 cells were treated with 0.125, 0.25, 0.50 or 1mg/ml of bevacizumab for 5 days. Proliferating HMVECad cells were maintained in culture with 50 ng/ml of Recombinant Human Vascular Endothelial Growth Factor (VEGF) while non-proliferating HMVECad cells were maintained in culture with 5 ng/ml of VEGF. HMVECad cells were treated with 0.125, 0.25, 0.50 or 1mg/ml of bevacizumab or 1mg/ml of a non-specific human purified immunoglobulin for 5 days. In order to assess mitochondrial function, mitochondrial dehydrogenase activity was determined using the WST-1 colorimetric assay.
After 5 days, 0.125 to 1mg/ml doses of bevacizumab did not significantly affect the mitochondrial dehydrogenase activity of ARPE-19 cells. The following doses: 0.50 and 1mg/ml (2 times and 4 times clinical dose respectively) of bevacizumab significantly reduced the mitochondrial dehydrogenase activity of R28 cells. All tested doses of bevacizumab significantly reduced the mitochondrial dehydrogenase activity of proliferating and non-proliferating HMVECad cells.
Bevacizumab at doses up to 4 times the clinical dose showed no significant toxicity to ARPE-19 cells in culture after 5 days exposure. In contrast rat neurosensory cells (R28) tolerated doses only up to the clinical dose of bevacizumab after 5 days exposure. The dose dependent decrease in mitochondrial dehydrogenase activity of proliferating and non-proliferating human microvascular endothelial (HMVECad) cells observed here in vitro at 5 days exposure, at all doses of bevacizumab including the clinical dose, is consistent with its known mechanism of action.
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