Effect of cediranib, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, in a mouse model of choroidal neovascularization.
ABSTRACT 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 (CNV). Methods: CNV 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, 1 mg/kg or 5 mg/kg of cediranib daily by oral gavage for two weeks. Two weeks after laser injury, the area of CNV lesions were measured by choroidal flat mounts using fluorescein-labeled dextran. Immunofluorescence staining with isolectin IB4 was also used to quantify the CNV lesions. Results: Choroidal flat mount analysis revealed that orally administered cediranib reduced the extent of CNV. The groups treated with 1 and 5 mg/kg/day showed 57.2 and 66.0 % reduction of CNV lesions, respectively, compared to the control group treated with vehicle alone (P = 0.012). The size of the fluorescently labeled CNV complex in cediranib-treated groups was much smaller than that from vehicle-treated group (P = 0.035). Conclusions: Cediranib inhibited laser-induced CNV in mice and may have therapeutic potential for patients with neovascular age-related macular degeneration. © 2012 The Authors. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.