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Inhibition of choroidal neovascularisation in mice by systemic administration of the multikinase inhibitor, sorafenib.

 E J Chung  ;  S Yoo  ;  H J Lim  ;  S H Byeon  ;  J H Lee  ;  H J Koh 
 BRITISH JOURNAL OF OPHTHALMOLOGY, Vol.93(7) : 958-963, 2009 
Journal Title
Issue Date
Administration, Oral ; Angiogenesis Inhibitors/administration & dosage* ; Animals ; Benzenesulfonates/administration & dosage* ; Blotting, Western ; Choroidal Neovascularization/drug therapy* ; Dextrans/administration & dosage ; Dose-Response Relationship, Drug ; Female ; Fluoresceins/administration & dosage ; Mice ; Mice, Inbred C57BL ; Niacinamide/analogs & derivatives ; Phenylurea Compounds ; Pyridines/administration & dosage*
BACKGROUND: To investigate the effect of orally administered sorafenib, a multikinase inhibitor, in a mouse model of choroidal neovascularisation (CNV).

METHODS: Sorafenib or vehicle was administered orally to female C57BL/6 mice at the onset (day 0) of experiments. CNV was induced by laser photocoagulation the following day. After 14 days, mice were perfused with fluorescein-labelled dextran, and the area of CNV was measured on choroidal flat mounts by image analysis. In some groups of mice, treatments were started 7 days after the laser photocoagulation to determine the effect of the agent on established CNV. Expression of phosphorylated extracellular signal-regulated kinase (p-ERK) in choroidal tissues was measured by Western blot analysis to demonstrate the kinase-inhibitory effect of sorafenib in intracellular signalling pathways involved in CNV formation.

RESULTS: Sorafenib significantly reduced the extent of CNV in a dose-dependent manner. The area of CNV was reduced by 43% in the 30 mg/kg/day group and by 61% in the 60 mg/kg/day group compared with vehicle-treated controls (both p<0.0001). Oral administration of sorafenib also caused significant regression of established CNV. The area of CNV was reduced by 59% in the 30 mg/kg/day group and by 66% in the 60 mg/kg/day group compared with both baseline and control measurements (p<0.0001). The expression of p-ERK in choroidal tissues was increased within 1 day of laser photocoagulation and remained elevated for 2 weeks. The expression of p-ERK was suppressed by sorafenib.

CONCLUSIONS: Sorafenib demonstrated antiangiogenic properties in a mouse model of CNV and may be useful in the treatment of CNV
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1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Koh, Hyoung Jun(고형준) ORCID logo https://orcid.org/0000-0002-5932-8516
Chung, Eun Jee(정은지)
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