title: Inhibition of corneal neovascularization in rats by systemic administration of sorafenib.
abstract: OBJECTIVE
  To evaluate the effect of orally administered sorafenib on corneal neovascularization in rat models.
  
  
  METHODS
  In male Sprague-Dawley rats, a silver nitrate applicator was placed on the central cornea in both eyes to elicit angiogenesis. Rats were divided into 3 groups, the control group and the 2 sorafenib-treated groups (low dose, 30 mg · kg(-1) · day(-1); high dose, 60 mg · kg(-1) · day(-1)). The area of corneal neovascularization was measured by image analysis. Vascular endothelial growth factor receptor 2 (VEGFR2) messenger RNA expression was measured in rat corneas by reverse transcription-polymerase chain reaction, and the expression of phosphorylated extracellular signal-regulated kinase (ERK) was measured by Western blot analysis 1 week after cauterization.
  
  
  RESULTS
  The area of corneal neovascularization was significantly reduced by 44% in the 30 mg · kg(-1) · day(-1) group and by 66% in the 60 mg · kg(-1) · day(-1) group, compared with the control group (P = 0.014 and P < 0.0001). Corneal VEGFR2 messenger RNA expression was higher in the control group than in the sorafenib-treated groups. The expression of phosphorylated ERK in rat corneas was suppressed in the sorafenib-treated groups but not in the control group.
  
  
  CONCLUSIONS
  Oral administration of a multikinase inhibitor (sorafenib) significantly reduced the development of experimental corneal neovascularization in a dose-dependent manner. This inhibitory effect is probably related to the suppression of ERK phosphorylation by sorafenib.
authors.affiliation: Department of Ophthalmology, Sahmyook Medical Center, Seoul Adventist Hospital, Seoul, Korea.
authors.forename: Jeong Won
authors.initials: JW
authors.lastname: Seo
authors.forename: So-Hyang
authors.initials: SH
authors.lastname: Chung
authors.forename: Jun-Sub
authors.initials: JS
authors.lastname: Choi
authors.forename: Choun-Ki
authors.initials: CK
authors.lastname: Joo
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001557:Benzenesulfonates / Q000008:administration & dosage* / Q000009:adverse effects; D015153:Blotting, Western; D016510:Corneal Neovascularization / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077157:Sorafenib; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics
chemical_list: D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D012333:RNA, Messenger; D009536:Niacinamide; D000077157:Sorafenib; D040301:Vascular Endothelial Growth Factor Receptor-2; D048049:Extracellular Signal-Regulated MAP Kinases