title: Effect of cediranib, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, in a mouse model of choroidal neovascularization.
abstract: BACKGROUND
  This study was conducted to evaluate the effect of cediranib, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, in a mouse model of laser-induced choroidal neovascularization.
  
  
  METHODS
  Choroidal neovascularization was induced in C57BL/6 mice by rupturing Bruch's membrane using laser photocoagulation. Following laser injury, the mice were divided into three groups and administered either vehicle, 1 mg/kg or 5 mg/kg of cediranib daily by oral gavage for 2 weeks. Two weeks after laser injury, the area of choroidal neovascularization lesions was measured by choroidal flat mounts using fluorescein-labelled dextran. Immunofluorescence staining with isolectin IB4 was also used to quantify the choroidal neovascularization lesions.
  
  
  RESULTS
  Choroidal flat mount analysis revealed that orally administered cediranib reduced the extent of choroidal neovascularization. The groups treated with 1 and 5 mg/kg/day showed 57.2 and 66.0% reduction of choroidal neovascularization lesions, respectively, compared with the control group treated with vehicle alone (P = 0.012). The size of the fluorescently labelled choroidal neovascularization complex in cediranib-treated groups was much smaller than that from vehicle-treated group (P = 0.035).
  
  
  CONCLUSIONS
  Cediranib inhibited laser-induced choroidal neovascularization in mice and may have therapeutic potential for patients with neovascular age-related macular degeneration.
authors.affiliation: Department of Ophthalmology and Visual Science, College of Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
authors.forename: Seungbum
authors.initials: S
authors.lastname: Kang
authors.forename: Ki Cheol
authors.initials: KC
authors.lastname: Park
authors.forename: Keum-Jin
authors.initials: KJ
authors.lastname: Yang
authors.forename: Hyun-Su
authors.initials: HS
authors.lastname: Choi
authors.forename: So-Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Young-Jung
authors.initials: YJ
authors.lastname: Roh
mesh_terms: D000284:Administration, Oral; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D015153:Blotting, Western; D020256:Choroidal Neovascularization / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D003911:Dextrans; D004195:Disease Models, Animal; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D019084:Fluorescent Antibody Technique, Indirect; D017075:Laser Coagulation; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D011799:Quinazolines / Q000008:administration & dosage / Q000627:therapeutic use*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*; D007211:Indoles
chemical_list: D020533:Angiogenesis Inhibitors; D003911:Dextrans; D016650:Fluorescein-5-isothiocyanate; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D011799:Quinazolines; D040301:Vascular Endothelial Growth Factor Receptor-2; C015219:fluorescein isothiocyanate dextran; C500926:cediranib; D007211:Indoles