title: Effect of bevacizumab (Avastin (TM) ) on mitochondrial function of in vitro retinal pigment epithelial, neurosensory retinal and microvascular endothelial cells.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Luthra
authors.forename: Ashish
authors.initials: A
authors.lastname: Sharma
authors.forename: Joyce
authors.initials: J
authors.lastname: Dong
authors.forename: Aneesh
authors.initials: A
authors.lastname: Neekhra
authors.forename: Ana L
authors.initials: AL
authors.lastname: Gramajo
authors.forename: Gail M
authors.initials: GM
authors.lastname: Seigel
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Kenney
authors.affiliation: Department of Ophthalmology, University of California, Irvine, California, USA, .
authors.forename: Baruch D
authors.initials: BD
authors.lastname: Kuppermann
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000068258:Bevacizumab; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008268:Macular Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008858:Microscopy, Phase-Contrast; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology*; D020419:Photoreceptor Cells, Vertebrate / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D012171:Retinal Vessels / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D014463:Ultrasonography; D042461:Vascular Endothelial Growth Factor A
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab