Effect of cediranib, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, in a mouse model of choroidal neovascularization

摘要

Background: This study was conducted to evaluate the effect of cediranib, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, in a mouse model of laser-induced choroidal neovascularization. Methods: Choroidal neovascularization was induced in C57BL/6 mice by rupturing Bruch's membrane using laser photocoagulation. Following laser injury, the mice were divided into three groups and administered either vehicle, 1mg/kg or 5mg/kg of cediranib daily by oral gavage for 2 weeks. Two weeks after laser injury, the area of choroidal neovascularization lesions was measured by choroidal flat mounts using fluorescein-labelled dextran. Immunofluorescence staining with isolectin IB4 was also used to quantify the choroidal neovascularization lesions. Results: Choroidal flat mount analysis revealed that orally administered cediranib reduced the extent of choroidal neovascularization. The groups treated with 1 and 5mg/kg/day showed 57.2 and 66.0% reduction of choroidal neovascularization lesions, respectively, compared with the control group treated with vehicle alone (P=0.012). The size of the fluorescently labelled choroidal neovascularization complex in cediranib-treated groups was much smaller than that from vehicle-treated group (P=0.035). Conclusions: Cediranib inhibited laser-induced choroidal neovascularization in mice and may have therapeutic potential for patients with neovascular age-related macular degeneration. Clinical and Experimental Ophthalmology