Different properties of VEGF-antagonists: Bevacizumab but not Ranibizumab accumulates in RPE cells

Graefes Arch Clin Exp Ophthalmol. 2009 Dec;247(12):1601-8. doi: 10.1007/s00417-009-1136-0. Epub 2009 Jul 14.


Background: Vascular endothelial growth factor (VEGF) antagonists are currently the therapy of choice for age-related macular degeneration. Here we compared the effects of FDA-approved Ranibizumab and off-label used Bevacizumab on RPE cells, investigating their respective uptake by RPE cells over time.

Methods: Primary porcine RPE cells were treated with Bevacizumab or Ranibizumab, respectively. Uptake of the respective VEGF-antagonists was assessed with confocal laser scanning microscopy and flow cytometry. Cell death was assessed with MTT assay and VEGF secretion was measured with ELISA.

Results: When clinical doses were applied for 1 h, Bevacizumab was taken up by RPE cells as assessed by confocal laser scanning microscopy and flow cytometry. After 24 h of incubation, and further assessed after 1d, 5d, and 7d, Bevacizumab was detected in RPE cells where it accumulated over time. The presence of Bevacizumab within RPE cells after 7d was confirmed by flow cytometry. While some Ranibizumab was found in RPE cells after 1 h of incubation when assessed with confocal laser microscopy but not by flow cytometry, no signal above control was detected after 1d, 5d, or 7d. Neither substance induced significant cell death after 7 days and no inhibitory effect on VEGF secretion was observed after day 3 of culture.

Conclusions: Bevacizumab, but not Ranibizumab, accumulates in RPE cells over time, implying substantial differences between these two drugs.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized
  • Bevacizumab
  • Cell Survival
  • Cells, Cultured
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Microscopy, Confocal
  • Organ Culture Techniques
  • Ranibizumab
  • Retinal Pigment Epithelium / drug effects*
  • Retinal Pigment Epithelium / metabolism
  • Swine
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / metabolism


  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Ranibizumab