Abstract |
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.
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Authors | Vivek K Gupta, Yuyi You, Jonathan C Li, Alexander Klistorner, Stuart L Graham |
Journal | Journal of molecular neuroscience : MN
(J Mol Neurosci)
Vol. 49
Issue 1
Pg. 96-104
(Jan 2013)
ISSN: 1559-1166 [Electronic] United States |
PMID | 23054592
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 6,7-dihydroxyflavone
- Flavones
- Neuroprotective Agents
- Receptor, trkB
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Topics |
- Animals
- Apoptosis
(drug effects)
- Flavones
(pharmacology)
- MAP Kinase Signaling System
- Neural Stem Cells
(drug effects, metabolism)
- Neurites
(drug effects)
- Neuroprotective Agents
(pharmacology)
- Oxidative Stress
- Phosphorylation
- Rats
- Rats, Sprague-Dawley
- Receptor, trkB
(agonists, metabolism)
- Retinal Ganglion Cells
(drug effects, metabolism)
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