Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 833, Issue -, Pages 283-289Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2018.06.007
Keywords
Reina; THF; Oxidative stress; Ocular hypertension; TrkB; Phosphorylation
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Funding
- Science and Technology Department, Henan Province [162102410063]
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In this study, we investigate the mechanism of 7,8,3'-Trihydroxyflavone (THF) on retinal oxidative stress and retinal ganglion cell (RGC) growth. Oxidative stress was induced by ocular hypertension (O.H.) in rat retina in vivo. Rats were then systemically injected with THF. We found THF ameliorated O.H.-induced oxidative stress in retina by reducing caspase-3 activity, downregulating MDA level and augmenting glutathione peroxidase expression. In addition, neonatal RGCs were cultured in vitro, and treated with THF. It was demonstrated that THF promoted neurite regeneration in RGC explant, and activated receptor kinase B (TrkB) signaling pathway through phosphorylation. In THF-treated RGC explant, application of TrkB antagonist, ANA12, effectively reversed the pro-neuronal effect of THF on promoting RGC neurite outgrowth, and inhibited TrkB signaling pathway through dephosphorylation. Thus, we concluded that THF could inhibit retinal oxidative stress and promote RGC growth through TrkB-dependent signaling pathway, thus providing a novel pharmaceutical candidate for glaucoma.
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