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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on October 29, 2007; DOI: 10.1124/jpet.107.132720

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Received for publication October 9, 2007.
Revised October 25, 2007.
Accepted for publication October 26, 2007.

Anti-angiogenic effect of deguelin on choroidal neovascularization

Jeong Hun Kim 1, Jin Hyoung Kim 1, Young Suk Yu 1*, Kyu Hyung Park 2, Hye Jin Kang 3, Ho-Young Lee 4, Kyu-Won Kim 3

1 Seoul National University Hospital 2 Bundang Seoul National University Hospital 3 Seoul National University 4 The University of Texas M. D. Anderson Cancer Center

* Address correspondence to: E-mail: ysyu{at}snu.ac.kr

Abstract

Age-related macular degeneration is the leading cause of blindness in elderly. choroidal neovascularization (CNV) leads to severe vision loss in patients of AMD. Previously, we have demonstrated that deguelin, isolated from plants in the Mundulea sericea family, is a chemo-preventive agent. This study is to evaluate the anti-angiogenic effect of deguelin on CNV. The toxicity of deguelin was evaluated through MTT assay in HUVECs as well as histological examination and TUNEL staining in the deguelin-injected retina. Anti-angiogenic activity of deguelin was evaluated by in vitro tube formation assay of human umbilical vein endothelial cells (HUVECs) and in vivo angiogenesis of chick chorioallantoic membrane (CAM). In C57BL/6 mice with laser-induced CNV, deguelin or PBS was injected intravitreously. CNV lesions were examined by fluorescence angiography and vessel counting in cross sections. Deguelin showed no affection to cell viability of HUVECs and no retinal toxicity in a concentration range of 0.01-1µM. 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 vaso-proliferative retinopathies such as retinopathy of prematurity and diabetic retinopathy.


Key words: Age-related macular degeneration, Anti-angiogenesis, Choroidal neovascularization, Deguelin, Retina, VEGF




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