title: Are intravitreal bevacizumab and ranibizumab effective in a rat model of choroidal neovascularization?
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.
authors.affiliation: Department of Ophthalmology and Visual Science, Yale University, School of Medicine, 40 Temple Street, Suite 3D, New Haven, CT 06510, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Lu
authors.forename: Ron A
authors.initials: RA
authors.lastname: Adelman
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D052157:Aptamers, Nucleotide / Q000494:pharmacology; D000068258:Bevacizumab; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005451:Fluorescein Angiography; D007267:Injections; D008028:Light Coagulation; D008268:Macular Degeneration / Q000188:drug therapy / Q000473:pathology; D000069579:Ranibizumab; D051381:Rats; D011914:Rats, Inbred BN; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014822:Vitreous Body
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D052157:Aptamers, Nucleotide; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; C495058:pegaptanib; D000068258:Bevacizumab; D000069579:Ranibizumab
references.citation: Arch Ophthalmol. 2002 Mar;120(3):338-46
references.pmid: 11879138
references.citation: Invest Ophthalmol Vis Sci. 2008 Feb;49(2):522-7
references.pmid: 18234994
references.citation: Invest Ophthalmol Vis Sci. 2007 Jun;48(6):2545-52
references.pmid: 17525183
references.citation: Invest Ophthalmol Vis Sci. 2007 Jun;48(6):2814-23
references.pmid: 17525217
references.citation: Invest Ophthalmol Vis Sci. 2000 Sep;41(10):3158-64
references.pmid: 10967078
references.citation: J Biol Chem. 1990 Dec 25;265(36):22071-4
references.pmid: 2266109
references.citation: Invest Ophthalmol Vis Sci. 2007 Dec;48(12):5708-15
references.pmid: 18055823
references.citation: Br J Ophthalmol. 1997 Feb;81(2):154-62
references.pmid: 9059252
references.citation: J Biol Chem. 2006 Mar 10;281(10):6625-31
references.pmid: 16373345
references.citation: Br J Ophthalmol. 2007 Jun;91(6):804-7
references.pmid: 17179168
references.citation: An Acad Bras Cienc. 2007 Sep;79(3):389-94
references.pmid: 17768531
references.citation: Ophthalmology. 1997 Jan;104(1):7-21
references.pmid: 9022098
references.citation: Vision Res. 1979;19(5):569-88
references.pmid: 483586
references.citation: Invest Ophthalmol Vis Sci. 2002 Jul;43(7):2384-91
references.pmid: 12091441
references.citation: Invest Ophthalmol Vis Sci. 2006 Feb;47(2):462-74
references.pmid: 16431938
references.citation: Invest Ophthalmol Vis Sci. 1999 Feb;40(2):459-66
references.pmid: 9950606
references.citation: Invest Ophthalmol Vis Sci. 1998 Feb;39(2):391-6
references.pmid: 9477999
references.citation: J Biol Chem. 1990 Nov 15;265(32):19461-6
references.pmid: 2246236
references.citation: Arch Ophthalmol. 2001 Mar;119(3):399-404
references.pmid: 11231773
references.citation: Growth Factors. 1992;7(1):53-64
references.pmid: 1380254
references.citation: Am J Ophthalmol. 2008 Feb;145(2):249-256
references.pmid: 18067876
references.citation: J Cell Physiol. 1991 Oct;149(1):50-9
references.pmid: 1719003