title: Antiangiogenic effects of topically administered multiple kinase inhibitor, motesanib (AMG 706), on experimental choroidal neovascularization in mice.
abstract: OBJECTIVE
  To investigate the effect of topical motesanib, an inhibitor of receptor tyrosine kinase, on experimental choroidal neovascularization (CNV).
  
  
  METHODS
  CNV was induced in 46 nine-week-old male C57BL/6 mice using fundus laser photocoagulation. The right eye of each mouse was treated with motesanib eye drop (4 times daily) and the left eye with vehicle eye drop (4 times daily) for 14 days. To evaluate changes in the CNV lesions, fluorescein angiography, immunofluorescence staining with CD34, and histological examinations were performed 14 days after CNV induction. The expression of phosphorylated extracellular signal-regulated kinase (ERK1/2) in choroidal tissues was determined using western blot analysis to demonstrate the inhibitory effect of topically administered motesanib on intracellular signaling pathways involved in CNV development.
  
  
  RESULTS
  Fluorescein angiography showed that fluorescence leakage in eyes treated with topical motesanib was significantly less than in mice treated with vehicle (P=0.01). On immunofluorescence staining, the CD34-labeled area was smaller in topical motesanib-treated eyes (P<0.001). The expression level of phosphorylated ERK1/2 relative to that of total ERK1/2 decreased in eyes treated with topical motesanib compared with eyes treated with vehicle.
  
  
  CONCLUSIONS
  Topical motesanib significantly reduced laser-induced CNV in the experimental mouse model.
authors.affiliation: 1 Department of Ophthalmology and Visual Science, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea , Daejeon, South Korea .
authors.forename: Chang Rae
authors.initials: CR
authors.lastname: Rho
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: Hyunsu
authors.initials: H
authors.lastname: Choi
authors.forename: Won-Kyung
authors.initials: WK
authors.lastname: Cho
mesh_terms: D000287:Administration, Topical; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D002829:Choroid / Q000098:blood supply* / Q000378:metabolism; D020256:Choroidal Neovascularization / Q000188:drug therapy*; D005451:Fluorescein Angiography; D007211:Indoles / Q000008:administration & dosage*; D017075:Laser Coagulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D023421:Models, Animal; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D009841:Oligonucleotides; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D009841:Oligonucleotides; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D048052:Mitogen-Activated Protein Kinase 3; C519562:imetelstat