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Inhibition of Hypoxia-Inducible Factor-1α and Vascular Endothelial Growth Factor by Chrysin in a Rat Model of Choroidal Neovascularization

Authors
 Ji Hun Song  ;  Ka Young Moon  ;  Sung Chul Lee  ;  Sung Soo Kim 
Citation
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.21(8) : 2842, 2020-04 
Journal Title
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 
Issue Date
2020-04
Keywords
age-related macular degeneration ; choroidal neovascularization ; chrysin ; hypoxia-inducible factor-1 alpha ; vascular endothelial growth factor
Abstract
Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among the elderly population. Vascular endothelial growth factor (VEGF) is essential for choroidal neovascularization (CNV) development in advanced, wet AMD. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid with anti-inflammatory, anti-oxidative, and anti-angiogenic effects. We hypothesized that intravitreally injected chrysin may inhibit CNV due to its inhibitory effect on angiogenesis. To determine the effects of chrysin on an experimental CNV model, we induced CNV in Brown Norway rats with a diode laser. One week later, rats were injected intravitreally with chrysin in the right eye and vehicle in the left eye. The following week, we evaluated chrysin's effects via the CNV grade assessed with fluorescein angiography and histologic analyses. Hypoxia-inducible factor-1 alpha (HIF-1α) and VEGF expression in the retina/choroid complex were also measured in both eyes. The mean CNV grade was significantly lower in chrysin-treated vs. control eyes (2.34 ± 1.14 vs. 2.97 ± 1.05, p < 0.001), as was the mean CNV thickness (33.90 ± 4.89 vs. 38.50 ± 5.43 μm, p < 0.001) and mean HIF-1α and VEGF levels (both p < 0.001). Compared to chrysin-treated eyes, the relative risk of control eyes developing high-leakage lesions was 2.03 (95% confidence interval: 1.46-2.83). Since chrysin inhibited laser-induced CNV and downregulated HIF-1α and VEGF expression, it is a candidate for treating wet AMD and other CNV-associated conditions.
DOI
10.3390/ijms21082842
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sung Soo(김성수) ORCID logo https://orcid.org/0000-0002-0574-7993
Lee, Sung Chul(이성철) ORCID logo https://orcid.org/0000-0001-9438-2385
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/179124
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