1. Academic Validation
  2. 7,8-Dihydroxyflavone protects retinal ganglion cells against chronic intermittent hypoxia-induced oxidative stress damage via activation of the BDNF/TrkB signaling pathway

7,8-Dihydroxyflavone protects retinal ganglion cells against chronic intermittent hypoxia-induced oxidative stress damage via activation of the BDNF/TrkB signaling pathway

  • Sleep Breath. 2022 Mar;26(1):287-295. doi: 10.1007/s11325-021-02400-5.
Yuan-Yuan Fang 1 Miao Luo 1 Shuang Yue 1 Yin Han 1 Huo-Jun Zhang 1 Yu-Hao Zhou 1 Kui Liu 1 Hui-Guo Liu 2
Affiliations

Affiliations

  • 1 Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
  • 2 Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China. huiguol@163.com.
Abstract

Purpose: Chronic intermittent hypoxia (CIH) plays a key role in the complications of obstructive sleep apnea (OSA), which is strongly associated with retinal and optic nerve diseases. Additionally, the brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling pathway plays an important protective role in neuronal injury. In the present study, we investigated the role of 7,8-dihydroxyflavone (7,8-DHF) in regulating CIH-induced injury in mice retinas and rat primary retinal ganglion cells (RGCs).

Methods: C57BL/6 mice and in vitro primary RGCs were exposed to CIH or normoxia and treated with or without 7,8-DHF. The mice eyeballs or cultured cells were then taken for Histochemistry, immunofluorescence or biochemistry, and the protein expression of the BDNF/TrkB signaling pathway analysis.

Results: Our results showed that CIH induced oxidative stress (OS) in in vivo and in vitro models and inhibited the conversion of BDNF precursor (pro-BDNF) to a mature form of BDNF, which increased neuronal cell Apoptosis. 7,8-DHF reduced the production of Reactive Oxygen Species (ROS) caused by CIH and effectively activated TrkB signals and downstream protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) survival signaling pathways, which upregulated the expression of mature BDNF. ANA-12 (a TrkB specific inhibitor) blocked the protective effect of 7,8-DHF.

Conclusion: In short, the activation of the BDNF/TrkB signaling pathway alleviated CIH-induced oxidative stress damage of the optic nerve and retinal ganglion cells. 7,8-DHF may serve as a promising agent for OSA related neuropathy.

Keywords

7,8-Dihydroxyflavone; Brain-derived neurotrophic factor; Chronic intermittent hypoxia; Oxidative stress; Retinal ganglion cells.

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