Effect of bevacizumab (Avastin™) on mitochondrial function of in vitro retinal pigment epithelial, neurosensory retinal and microvascular endothelial cells.
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Date
2013-12
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Abstract
Purpose: To evaluate the effect of bevacizumab on the mitochondrial function of human retinal pigment
epithelial (ARPE‑19), rat neurosensory retinal (R28) and human microvascular endothelial (HMVEC) cells
in culture. Materials and Methods: ARPE‑19 and R28 cells were treated with 0.125, 0.25, 0.50 and 1 mg/ml
of bevacizumab. The HMVEC cultures were treated with 0.125, 0.25, 0.50 and 1 mg/ml of bevacizumab or
1 mg/ml of immunoglobulin G (control). Mitochondrial function assessed by mitochondrial dehydrogenase
activity (MDA) was determined using the WST‑1 assay. Results: Bevacizumab doses of 0.125 to
1 mg/ml for 5 days did not significantly affect the MDA of ARPE‑19 cells. Bevacizumab treatment at 0.125
and 0.25 mg/ml (clinical dose) did not significantly affect the MDA of R28 cells; however, 0.50 and 1 mg/ml
doses significantly reduced the R28 cell mitochondrial function. All doses of bevacizumab significantly
reduced the MDA of proliferating and non‑proliferating HMVEC. Conclusion: Bevacizumab exposure
for 5 days was safe at clinical doses in both ARPE‑19 and R28 retinal neurosensory cells in culture. By
contrast, bevacizumab exposure at all doses show a significant dose‑dependent decrease in mitochondrial
activity in both the proliferating and non‑proliferating HMVEC in vitro. This suggests a selective action of
bevacizumab on endothelial cells at clinical doses.
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Keywords
Bevacizumab, mitochondrial function, microvascular endothelial cells, neurosensory retinal cells, retinal pigment epithelial cells, tissue culture
Citation
Luthra Saurabh, Sharma Ashish, Dong Joyce, Neekhra Aneesh, Gramajo Ana L, Seigel Gail M, Cristina Kenney M, Kuppermann Baruch D. Effect of bevacizumab (Avastin™) on mitochondrial function of in vitro retinal pigment epithelial, neurosensory retinal and microvascular endothelial cells. Indian Journal of Ophthalmology. 2013 Dec ; 61 (12): 705-710.