Antiangiogenic effect of deguelin on choroidal neovascularization

Abstract

Age-related macular degeneration is the leading cause of blindness in the elderly. Choroidal neovascularization (CNV) leads to severe vision loss in patients of age-related macular degeneration. Previously, we have demonstrated that deguelin, isolated from plants in the Mundulea sericea family, is a chemopreventive agent. This study evaluates the antiangiogenic effect of deguelin on CNV. The toxicity of deguelin was evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in human umbilical vein endothelial cells (HUVECs) as well as histological examination and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining in the deguelin-injected retina. Antiangiogenic activity of deguelin was evaluated by in vitro tube formation assay of HUVECs and in vivo angiogenesis of chick chorioallantoic membrane (CAM). In C57BL/6 mice with laser-induced CNV, deguelin or phosphate-buffered saline was injected intravitreously. CNV lesions were examined by fluorescence angiography and vessel counting in cross-sections. Deguelin showed no effect on cell viability of HUVECs and no retinal toxicity in a concentration range of 0.01 to 1 microM. Deguelin effectively inhibited in vitro tube formation of HUVECs and in vivo angiogenesis of CAM. Interestingly, deguelin significantly reduced CNV and its leakage in mouse model of laser photocoagulation-induced CNV. Our data suggests that deguelin is a potent inhibitor of CNV and may be applied in the treatment of other vasoproliferative retinopathies such as retinopathy of prematurity and diabetic retinopathy.