Retinal Ganglion Cell Loss is Delayed Following Optic Nerve Crush in NLRP3 Knockout Mice.
Retinal Ganglion Cell Loss is Delayed Following Optic Nerve Crush in NLRP3 Knockout Mice.
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DOI：
10.1038/srep20998
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发表时间：
2016-02-19
影响因子：
4.6
通讯作者：
Liu X
中科院分区：
文献类型：
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作者：
Puyang Z;Feng L;Chen H;Liang P;Troy JB;Liu X
NLRP3炎症小体是多种病原体和宿主源性威胁的传感器，由适配器ASC（含有Caspase激活和募集结构域（CARD）的凋亡相关斑点样蛋白）、前Caspase -1和NLRP3 （nod样受体家族Pyrin结构域包含3）组成。NLRP3诱导的神经炎症与眼病的发病和进展有关，但目前尚不清楚NLRP3炎症小体的激活是否导致视网膜神经节细胞（RGC）死亡。在这里，我们研究了nlrp3诱导的神经炎症和部分视神经压迫（pONC）损伤后的RGC存活。我们发现，在pONC后，NLRP3在视网膜小胶质细胞中表达上调，并在一天内从损伤部位传播到视神经头，最终传播到整个视网膜。NLRP3-ASC炎性小体的激活导致caspase-1和促炎细胞因子白介素-1β (IL-1β)的上调。在NLRP3敲除小鼠中，ASC、caspase-1和IL-1β的上调均降低，重要的是，pONC损伤后，RGC和轴突损失明显延迟。NLRP3基因敲除小鼠中RGCs的平均存活时间比对照动物长约一周。综上所述，我们的研究表明，切除NLRP3基因可显著减少视神经挤压损伤后的神经炎症和延迟RGC丢失。
The NLRP3 inflammasome, a sensor for a variety of pathogen- and host-derived threats, consists of the adaptor ASC (Apoptosis-associated Speck-like protein containing a Caspase Activation and Recruitment Domain (CARD)), pro-caspase-1, and NLRP3 (NOD-Like Receptor family Pyrin domain containing 3). NLRP3-induced neuroinflammation is implicated in the pathogenesis and progression of eye diseases, but it remains unclear whether activation of NLRP3 inflammasome contributes to retinal ganglion cell (RGC) death. Here we examined NLRP3-induced neuroinflammation and RGC survival following partial optic nerve crush (pONC) injury. We showed that NLRP3 was up-regulated in retinal microglial cells following pONC, propagating from the injury site to the optic nerve head and finally the entire retina within one day. Activation of NLRP3-ASC inflammasome led to the up-regulation of caspase-1 and a proinflammatory cytokine, interleukin-1β (IL-1β). In NLRP3 knockout mice, up-regulation of ASC, caspase-1, and IL-1β were all reduced, and, importantly, RGC and axon loss was substantially delayed following pONC injury. The average survival time of RGCs in NLRP3 knockout mice was about one week longer than for control animals. Taken together, our study demonstrated that ablating the NLRP3 gene significantly reduced neuroinflammation and delayed RGC loss after optic nerve crush injury.