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

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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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Acknowledgments

Support funds from the Ophthalmic Research Institute of Australia, National Multiple Sclerosis Society, Multiple Sclerosis Research Australia, and MQNS grant are gratefully acknowledged. RGC-5 cells were kindly provided by Prof. Al-Ubaidi, University of Oklahoma. VG was supported by funding from Allergan Australia.

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Authors and Affiliations

  1. Australian School of Advanced Medicine, Macquarie University, F10A, Level 1, 2 Technology Place, North Ryde, Sydney, NSW, 2109, Australia

    Vivek K. Gupta, Yuyi You, Jonathan C. Li, Alexander Klistorner & Stuart L. Graham

  2. Save Sight Institute, Sydney University, Sydney, Australia

    Alexander Klistorner & Stuart L. Graham

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  1. Vivek K. Gupta
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  2. Yuyi You
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  3. Jonathan C. Li
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  4. Alexander Klistorner
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  5. Stuart L. Graham
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Correspondence to Vivek K. Gupta.

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Vivek K. Gupta, Yuyi You, and Jonathan C Li contributed equally to the work.

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Gupta, V.K., You, Y., Li, J.C. et al. Protective Effects of 7,8-Dihydroxyflavone on Retinal Ganglion and RGC-5 Cells Against Excitotoxic and Oxidative Stress. J Mol Neurosci 49, 96–104 (2013). https://doi.org/10.1007/s12031-012-9899-x

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  • DOI: https://doi.org/10.1007/s12031-012-9899-x

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