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15.05.2021 | Sleep Breathing Physiology and Disorders • Original Article

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

verfasst von: Yuan-yuan Fang, Miao Luo, Shuang Yue, Yin Han, Huo-jun Zhang, Yu-hao Zhou, Kui Liu, Hui-guo Liu

Erschienen in: Sleep and Breathing | Ausgabe 1/2022

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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.

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Titel: 7,8-Dihydroxyflavone protects retinal ganglion cells against chronic intermittent hypoxia-induced oxidative stress damage via activation of the BDNF/TrkB signaling pathway
verfasst von: Yuan-yuan Fang
Miao Luo
Shuang Yue
Yin Han
Huo-jun Zhang
Yu-hao Zhou
Kui Liu
Hui-guo Liu
Publikationsdatum: 15.05.2021
Verlag: Springer International Publishing
Erschienen in: Sleep and Breathing / Ausgabe 1/2022
Print ISSN: 1520-9512
Elektronische ISSN: 1522-1709
DOI: https://doi.org/10.1007/s11325-021-02400-5

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

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Conclusion

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