TY - JOUR T1 - Inhibition of choroidal neovascularisation in mice by systemic administration of the multikinase inhibitor, sorafenib JF - British Journal of Ophthalmology JO - Br J Ophthalmol SP - 958 LP - 963 DO - 10.1136/bjo.2008.149187 VL - 93 IS - 7 AU - E J Chung AU - S Yoo AU - H J Lim AU - S H Byeon AU - J H Lee AU - H J Koh Y1 - 2009/07/01 UR - http://bjo.bmj.com/content/93/7/958.abstract N2 - 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. ER -