文章基本信息

标题：Assessment of intrinsic and extrinsic signaling pathway in excitotoxic retinal ganglion cell death
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作者：Berkeley K. Fahrenthold ; Kimberly A. Fernandes ; Richard T. Libby 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2018
卷号：8
期号：1
页码：4641
DOI：10.1038/s41598-018-22848-y
语种：English
出版社：Springer Nature
摘要：Excitotoxicity leads to the activation of a cytotoxic cascade that causes neuronal death. In the retina, retinal ganglion cells (RGCs) die after an excitotoxic insult. Multiple pathways have been proposed to contribute to RGC death after an excitotoxic insult, including TNF signaling, JNK activation, and ER stress. To test the importance of these pathways in RGC death after excitotoxic injury, the excitotoxin N-methyl-D-aspartate (NMDA) was intravitreally injected into mice deficient in components of these pathways. Absence of Tnf or its canonical downstream mediator, Bid, did not confer short- or long-term protection to RGCs. Despite known activation in RGCs and a prominent role in mediating RGC death after other insults, attenuating JNK signaling did not prevent RGC death after excitotoxic insult. Additionally, deficiency of the ER stress protein DDIT3 (CHOP), which has been shown to be involved in RGC death, did not lessen NMDA induced RGC death. Furthermore, absence of both Jun (JNK's canonical target) and Ddit3, which together provide robust, long-term protection to RGC somas after axonal insult, did not lessen RGC death. Collectively, these results indicate that the drivers of excitotoxic injury remain to be identified and/or multiple cell death pathways are activated in response to injury.