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Resveratrol inhibits hypoxia-induced vascular endothelial growth factor expression and choroidal neovascularization

Other Titles
 레스베라트롤은 저산소증에 의한 혈관 내피 성장 인자의 발현 및 맥락막 신생 혈관을 억제 
Authors
 이승규 
Issue Date
2014
Description
Dept. of Medicine/박사
Abstract
Purpose. To investigate the effects of resveratrol on the expression of hypoxia–inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) in human adult retinal pigment epithelial (ARPE) cells, and on experimental choroidal neovascularization (CNV) in mice. Methods. Human retinal pigment epithelial cells (ARPE-19) were treated with different concentrations of resveratrol and incubated under hypoxic conditions with subsequent evaluation of cell viability, expression of HIF-1α, and expression of VEGF. In the same cells, the effects of resveratrol on the synthesis and degradation of hypoxia-induced HIF-1α were evaluated using inhibitors of the PI3K/Akt/mTOR and the ubiquitin proteasome pathways. In animal studies, CNV lesions were induced in C57BL/6 mice by laser photocoagulation. After 7 days of oral administration of resveratrol or vehicle, which began one day after CNV induction, image analysis was used to measure CNV areas on choroidal flat mounts stained with isolectin IB4. Results. In ARPE-19 cells, resveratrol significantly inhibited hypoxia-induced increases of HIF-1α and VEGF in a dose-dependent manner, by blocking the PI3K/Akt/mTOR signaling pathway and by promoting proteasomal HIF-1α degradation. In mice experiments, orally administered resveratrol significantly inhibited CNV growth in a dose-dependent manner. Conclusions. Resveratrol effectively inhibited the accumulation of hypoxia-induced HIF-1α and VEGF in ARPE-19 cells, and inhibited the progression of experimental CNV in mice, suggesting resveratrol’s therapeutic value in the management of neovascular AMD.
Full Text
https://ymlib.yonsei.ac.kr/catalog/search/book-detail/?cid=CAT000000198189
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Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 3. Dissertation
Yonsei Authors
Lee, Christopher Seungkyu(이승규) ORCID logo https://orcid.org/0000-0001-5054-9470
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/135110
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