Protective Effects of 7,8-Dihydroxyflavone on Retinal Ganglion and RGC-5 Cells Against Excitotoxic and Oxidative Stress

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• 作者：Vivek K. Gupta (1)
  Yuyi You (1)
  Jonathan C. Li (1)
  Alexander Klistorner (1) (2)
  Stuart L. Graham (1) (2)
  
• 关键词：Retinal ganglion cells ; 7 ; 8 ; Dihydroxyflavone ; TrkB receptor ; Brain ; derived neurotrophic factor ; Cell signaling
• 刊名：Journal of Molecular Neuroscience
• 出版年：2013
• 出版时间：January 2013
• 年：2013
• 卷：49
• 期：1
• 页码：96-104
• 全文大小：473KB
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• 作者单位：Vivek K. Gupta (1)
  Yuyi You (1)
  Jonathan C. Li (1)
  Alexander Klistorner (1) (2)
  Stuart L. Graham (1) (2)
  
  1. Australian School of Advanced Medicine, Macquarie University, F10A, Level 1, 2 Technology Place, North Ryde, Sydney, NSW, 2109, Australia
  2. Save Sight Institute, Sydney University, Sydney, Australia
  

文摘

A preferential loss of retinal ganglion cells (RGCs) is observed in glaucoma and optic neuritis. Loss of tropomyosin-related kinase receptor B (TrkB)-mediated signaling has been implicated in this degeneration. Our study indicates that 7,8-dihydroxyflavone (7,8 DHF) robustly upregulates the TrkB signaling in the primary rat RGCs and the retinal neuronal precursor RGC-5 cell line by promoting phosphorylation of TrkB receptor, leading to enhanced TrkB receptor tyrosine kinase activity. The flavonoid derivative 7,8 DHF acts a potent TrkB agonist and upregulates the downstream AKT and MAPK/ERK survival signaling pathways in a TrkB-dependent manner in both primary rat RGCs as well as the RGC-5 cell line. Excitotoxicity and oxidative injury have been alleged in the specific RGC degeneration in various forms of glaucoma. A novel finding of this study is that treatment with 7,8 DHF protects these cells significantly from excitotoxic and oxidative stress-induced apoptosis and cell death. 7,8 DHF also promotes neuritogenesis by stimulating neurite outgrowth, suggesting a possible therapeutic strategy for protection of RGCs in various optic neuropathies.