Laquinimod exerts anti-inflammatory and antiapoptotic effects in retinal ischemia/reperfusion injury
Laquinimod exerts anti-inflammatory and antiapoptotic effects in retinal ischemia/reperfusion injury
复制标题
拉喹莫德在视网膜缺血/再灌注损伤中发挥抗炎和抗凋亡作用
DOI：
10.1016/j.intimp.2020.106989
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发表时间：
2020-11-01
影响因子：
5.6
通讯作者：
Zhuo, Yehong
中科院分区：
文献类型：
--
作者：
Jiang, Nan;Li, Zhidong;Zhuo, Yehong
Retinal ischemia/reperfusion (I/R) occurs in various vision disabled ocular diseases, involved in acute glaucoma, diabetic retinopathy, ischemic optic neuropathy, hypertensive retinopathy and retinal vascular occlusion. Laquinimod (LQ), a new type of immunosuppressant, has been reported to exert anti-inflammatory effects on autoimmune diseases. This research aims to investigate the protective effect of LQ on I/R damage by focusing on inhibiting dysregulated neuroinflammation and neuronal apoptosis. In our study, mice were treated with LQ after high intraocular pressure (IOP)-induced retinal I/R injury. The data showed that LQ significantly attenuated high IOP-induced retinal ganglion cell (RGC) death and inner plexiform layer (IPL) thinning and inhibited microglial activation. The results of qRT-PCR, flow cytometry and Luminex multiplex assays demonstrated the anti-inflammatory action of LQ in BV2 cells stimulated with lipopolysaccharide (LPS). In addition, primary RGC apoptosis induced by oxygen-glucose deprivation/reperfusion (OGD/R) was also directly suppressed by LQ. Importantly, LQ inhibited the expression of cleaved caspase-8 and the downstream NLRP3 inflammasome and IL-1 beta. In conclusion, our findings offer the first evidence that LQ treatment prevents retinal I/R damage. Furthermore, LQ could directly inhibit RGC apoptosis. Caspase-8 activation and subsequent inflammation can also be suppressed by LQ, which suggests that LQ may act through inhibiting the caspase-8 pathway. This study demonstrates a new mechanism of LQ and provides beneficial preclinical data for the clinical application of LQ.
