Purpose: To investigate the effects of axitinib, an inhibitor of vascular endothelial growth factor receptors, on choroidal neovascularization (CNV) in an animal model of neovascular age-related macular degeneration (AMD).
Methods: Experimental CNV lesions were induced in C57BL/6 mice by laser photocoagulation. Beginning 1 day after CNV induction, mice were treated with axitinib (5 mg/kg/day) or vehicle for 2 weeks. In other groups of mice, axitinib or vehicle treatment was started 7 days after the laser application to determine the effect of the drug on established CNV. Untreated mice were used as a baseline group. Two weeks after laser injury, the extent of CNV was assessed from choroidal flat mounts perfused with fluorescein-labeled dextran. Immunofluorescence staining with isolectin IB4 was also used to quantify the CNV lesions.
Results: Orally administered axitinib inhibited CNV growth in the laser-induced CNV model. Axitinib caused a 70.1% inhibition of CNV lesions compared to vehicle-treatment (p < 0.001). Axitinib also caused a significant regression of established CNV, reducing the area by 71.1% compared to vehicle treatment (p < 0.001). Moreover, immunofluorescence staining showed that the area of isolectin IB4 labeled vessels was smaller in the axitinib-treated group compared to the vehicle-treated group (p < 0.001).
Conclusions: Axitinib effectively inhibits the progression of CNV in an experimental animal model. These results suggest that axitinib could constitute a therapeutic alternative for the treatment of neovascular AMD.