Are intravitreal bevacizumab and ranibizumab effective in a rat model of choroidal neovascularization?

Graefes Arch Clin Exp Ophthalmol. 2009 Feb;247(2):171-7. doi: 10.1007/s00417-008-0936-y. Epub 2008 Sep 10.

Abstract

Background: Vascular endothelial growth factor (VEGF) is an important stimulator of choroidal neovascularization (CNV). Bevacizumab (Avastin), ranibizumab (Lucentis) and pegaptanib sodium (Macugen) are anti-VEGF medications that have been used in the treatment of CNV. The purpose of our study is to evaluate the efficacy and safety of intravitreal injections of bevacizumab, ranibizumab and pegaptanib sodium in the treatment of CNV in a rat model.

Methods: Multiple CNV lesions were induced by laser photocoagulation of the retina in Brown-Norway rats. After 3 weeks, 17 rats were divided into three groups and received intravitreal injections of bevacizumab, ranibizumab or pegaptanib sodium in different dosages. The lesions were evaluated by fluorescein angiography 1, 7, 14, and 28 days later to assess the efficacy of these medications.

Results: Different doses of bevacizumab did not show any effect on stopping the leakage on fluorescein angiography on days 1, 7, 14, and 28. Ranibizumab and pegaptanib sodium did not stop the leakage of CNV either. No angiographic or histopathologic toxicity was observed.

Conclusions: These three anti-VEGF agents did not show any therapeutic effect on stopping CNV leakage in rats. Previous experiments with ranibizumab in monkeys resulted in a significant decrease in leakage of CNV. The difference may be due to the fact that both ranibizumab and bevacizumab are humanized and species-specific. There are several studies evaluating the effect of bevacizumab in non-primates. Since bevacizumab is humanized, the results of studies on non-primates may not be similar to humans and non-human primates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized
  • Aptamers, Nucleotide / pharmacology
  • Bevacizumab
  • Choroidal Neovascularization / drug therapy*
  • Choroidal Neovascularization / pathology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Fluorescein Angiography
  • Injections
  • Light Coagulation
  • Macular Degeneration / drug therapy
  • Macular Degeneration / pathology
  • Ranibizumab
  • Rats
  • Rats, Inbred BN
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vitreous Body

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Aptamers, Nucleotide
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • pegaptanib
  • Bevacizumab
  • Ranibizumab