title: 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.
authors.affiliation: Department of Ophthalmology, College of Medicine, Seoul National University and Seoul Artificial Eye Center Clinical Research Institute, Seoul National University Hospital, Seoul 151-744, Republic of Korea.
authors.forename: Jeong Hun
authors.initials: JH
authors.lastname: Kim
authors.forename: Jin Hyoung
authors.initials: JH
authors.lastname: Kim
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Yu
authors.forename: Kyu Hyung
authors.initials: KH
authors.lastname: Park
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Kang
authors.forename: Ho-Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Kyu-Won
authors.initials: KW
authors.lastname: Kim
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002829:Choroid / Q000098:blood supply / Q000187:drug effects; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D012402:Rotenone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D012402:Rotenone; C107676:deguelin