Inhibition of hypoxia-inducible factor-1α and vascular endothelial growth factor by chrysin in a rat model of choroidal neovascularization

Ji Hun Song, Ka Young Moon, Sung Chul Lee, Sung Soo Kim

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10 Citations (Scopus)


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.

Original languageEnglish
Article number2842
JournalInternational journal of molecular sciences
Issue number8
Publication statusPublished - 2020 Apr 2

Bibliographical note

Funding Information:
Funding: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. NRF-2018R1C1B5044824).

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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