title: Antiangiogenic effects of axitinib, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, on laser-induced choroidal neovascularization in mice.
abstract: OBJECTIVE
  To investigate the effects of axitinib, an inhibitor of vascular endothelial growth factor receptors, on choroidal neovascularization (CNV) in an animal model of neovascular age-related macular degeneration (AMD).
  
  
  METHODS
  Experimental CNV lesions were induced in C57BL/6 mice by laser photocoagulation. Beginning 1 day after CNV induction, mice were treated with axitinib (5 mg/kg/day) or vehicle for 2 weeks. In other groups of mice, axitinib or vehicle treatment was started 7 days after the laser application to determine the effect of the drug on established CNV. Untreated mice were used as a baseline group. Two weeks after laser injury, the extent of CNV was assessed from choroidal flat mounts perfused with fluorescein-labeled dextran. Immunofluorescence staining with isolectin IB4 was also used to quantify the CNV lesions.
  
  
  RESULTS
  Orally administered axitinib inhibited CNV growth in the laser-induced CNV model. Axitinib caused a 70.1% inhibition of CNV lesions compared to vehicle-treatment (p < 0.001). Axitinib also caused a significant regression of established CNV, reducing the area by 71.1% compared to vehicle treatment (p < 0.001). Moreover, immunofluorescence staining showed that the area of isolectin IB4 labeled vessels was smaller in the axitinib-treated group compared to the vehicle-treated group (p < 0.001).
  
  
  CONCLUSIONS
  Axitinib effectively inhibits the progression of CNV in an experimental animal model. These results suggest that axitinib could constitute a therapeutic alternative for the treatment of neovascular AMD.
authors.affiliation: Department of Ophthalmology and Visual Science, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Korea.
authors.forename: Seungbum
authors.initials: S
authors.lastname: Kang
authors.forename: Chang Rae
authors.initials: CR
authors.lastname: Roh
authors.forename: Won-Kyung
authors.initials: WK
authors.lastname: Cho
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: D000818:Animals; D000077784:Axitinib; D002829:Choroid / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology; D004195:Disease Models, Animal; D007093:Imidazoles / Q000627:therapeutic use*; D007191:Indazoles / Q000627:therapeutic use*; D017075:Laser Coagulation / Q000009:adverse effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors*
chemical_list: D007093:Imidazoles; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D000077784:Axitinib; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1