Protective effects of 7,8-dihydroxyflavone on retinal ganglion and RGC-5 cells against excitotoxic and oxidative stress.
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.
Australian School of Advanced Medicine, Macquarie University, F10A, Level 1, 2 Technology Place, North Ryde, Sydney, NSW 2109, Australia. vivek.gupta@mq.edu.au
Vivek K
VK
Gupta
Yuyi
Y
You
Jonathan C
JC
Li
Alexander
A
Klistorner
Stuart L
SL
Graham
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D047309:Flavones / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism; D016501:Neurites / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000819:agonists / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism
C485383:6,7-dihydroxyflavone; D047309:Flavones; D018696:Neuroprotective Agents; D020813:Receptor, trkB