Background: To investigate the effect of orally administered sorafenib (Nexavar®, Bay-43-9006, Bayer Schering Pharma, Germany), a multikinase inhibitor, in a mouse model of choroidal neovascularization (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-labeled 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 signaling 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 anti-angiogenic properties in a mouse model of CNV and may be useful in the treatment of CNV.