Abstract
Hypoxia-induced retinal ganglion cell (RGC) death has been proposed to be the critical event in the pathophysiology of glaucoma. Therefore, delaying or halting RGC degeneration, known as neuroprotection, is a novel and promising approach with potential clinical applications for treating glaucoma. In this study, we investigate hypoxia-induced cell death of RGCs and the underlying mechanisms of N-acetylcysteine (NAC) as a neuroprotectant. To establish a model for chemical hypoxia-induced cell death, RGC-5 cells were treated with the hypoxia mimetic cobalt chloride (CoCl2). Following CoCl2 exposure, significant levels of apoptotic and autophagic cell death were observed in RGC-5 cells, evidenced by lysosome dysfunction and autophagosome formation. Pretreating RGC-5 cells with NAC significantly counteracted the autophagic cell death. NAC-mediated neuroprotection was attributed to the direct scavenging of reactive oxygen species and was mediated by targeting the hypoxia-inducible factor-1α pathway via the BNIP3 and PI3K/Akt/mTOR pathways. These results provide insights into the degeneration of RGCs and present a potential clinical application for NAC as a neuroprotectant.
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Acknowledgments
This study was supported by the National Key Basic Research Program (2010CB529800), the National Natural Science Foundation of China (No. 30472012, 30700280 and 30701018), the Shanghai Municipal Science and Technology Commission (No. 11ZR1419300), the Shanghai Municipal Education Commission (No. 12YZ037), and the Shanghai Leading Academic Discipline Project (No. S30205).
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Lan Yang and Panpan Tan contributed equally to this work.
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Yang, L., Tan, P., Zhou, W. et al. N-Acetylcysteine Protects Against Hypoxia Mimetic-Induced Autophagy by Targeting the HIF-1α Pathway in Retinal Ganglion Cells. Cell Mol Neurobiol 32, 1275–1285 (2012). https://doi.org/10.1007/s10571-012-9852-0
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DOI: https://doi.org/10.1007/s10571-012-9852-0