Effect of bevacizumab (Avastin™) on mitochondrial function of in vitro retinal pigment epithelial, neurosensory retinal and microvascular endothelial cells.

Luthra, Saurabh; Sharma, Ashish; Dong, Joyce; Neekhra, Aneesh; Gramajo, Ana L; Seigel, Gail M; Kenney, M Cristina; Kuppermann, Baruch D

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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