May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Effect of Bevacizumab (AvastinTM) on Mitochondrial Function of Retinal Pigment Epithelial, Neurosensory Retinal and Microvascular Endothelial Cells in Culture
Author Affiliations & Notes
  • S. Luthra
    Ophthalmology, Drishti Eye Centre, Dehradun, India
    Ophthalmology, University of California Irvine, Irvine, California
  • J. Dong
    Ophthalmology, University of California Irvine, Irvine, California
  • A. Neekhra
    Ophthalmology, University of California Irvine, Irvine, California
  • A. L. Gramajo
    Ophthalmology, University of California Irvine, Irvine, California
  • G. M. Seigel
    Ophthalmology, The Ross Eye Institute, University at Buffalo, SUNY, Buffalo, New York
  • D. J. Brown
    Ophthalmology, University of California Irvine, Irvine, California
  • M. C. Kenney
    Ophthalmology, University of California Irvine, Irvine, California
  • B. D. Kuppermann
    Ophthalmology, University of California Irvine, Irvine, California
  • Footnotes
    Commercial Relationships S. Luthra, None; J. Dong, None; A. Neekhra, None; A.L. Gramajo, None; G.M. Seigel, None; D.J. Brown, None; M.C. Kenney, None; B.D. Kuppermann, None.
  • Footnotes
    Support PAAO Foundation(David & Julianna Pyott Pan-American Retinal Research Fellowship), Discovery Eye Foundation, Skirball Molecular Ophthalmology Program,Iris and B. Gerald Cantor Foundation,RPB Foundation
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 2197. doi:
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    • Get Citation

      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)

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Abstract

Purpose:: 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.

Methods:: 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.

Results:: 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.

Conclusions:: 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.

Keywords: age-related macular degeneration • drug toxicity/drug effects • retinal culture 
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