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Rosmarinic acid suppresses retinal neovascularization via cell cycle arrest with increase of p21(WAF1) expression

Cited 29 time in Web of Science Cited 30 time in Scopus
Authors
Kim, Jeong Hun; Lee, Byung Joo; Kim, Jin Hyoung; Yu, Young Suk; Kim, Kyu-Won; Kim, Min Young
Issue Date
2009-08-01
Publisher
ELSEVIER SCIENCE BV
Citation
EUROPEAN JOURNAL OF PHARMACOLOGY; Vol.615 1-3; 150-154
Keywords
Anti-angiogenesisRetinopathy of prematurityRosmarinic acidRetinal neovascularizationCell cycle arrestp21(WAF1)
Abstract
Pathological angiogenesis is the most common cause of blindness at all ages including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration. Despite advances in therapy, retinopathy of prematurity remains the most sight-threatening vaso-proliferative retinopathy in children. Herein, we demonstrated that rosmarinic acid has an anti-angiogenic activity to retinal neovascularization in a mouse model of retinopathy of prematurity, which is related to cell cycle arrest with increase of p21(WAF1). Rosmarinic acid significantly inhibited the proliferation of retinal endothelial cells in a dose-dependent manner, and inhibited in vitro angiogenesis of tube formation. Interestingly, the anti-proliferative activity of rosmarinic acid on retinal endothelial cells was related to G(2)/M phase cell cycle arrest in a dose-dependent manner. With treatment of rosmarinic acid, retinal endothelial cells in G(2)/M phase increased whereas those in G(0)/G(1) and S phases decreased, which was accompanied by increase of p21(WAF1) expression in a dose-dependent manner. Moreover, rosmarinic acid effectively suppressed retinal neovascularization in a mouse model of retinopathy of prematurity, and showed no retinal toxicity. These data suggest rosmarinic acid could be a potent inhibitor of retinal neovascularization and may be applied in the treatment of other vasoproliferative retinopathie s. (C) 2009 Elsevier B.V. All rights reserved.
ISSN
0014-2999
Language
English
URI
http://hdl.handle.net/10371/77978
DOI
https://doi.org/10.1016/j.ejphar.2009.05.015
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College of Medicine/School of Medicine (의과대학/대학원)Ophthalmology (안과학전공)Journal Papers (저널논문_안과학전공)
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