Interleukin-35 suppresses pyroptosis and protects against neuronal death in retinal ischaemia/reperfusion injury
Interleukin-35 suppresses pyroptosis and protects against neuronal death in retinal ischaemia/reperfusion injury
复制标题
Interleukin-35 抑制视网膜缺血/再灌注损伤中的细胞焦亡并防止神经元死亡
DOI：
10.1016/j.exer.2022.109109
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发表时间：
2022-05-21
影响因子：
3.4
通讯作者：
Zhuo, Yehong
中科院分区：
文献类型：
--
作者：
Lin, Bingying;Li, Yangyang;Zhuo, Yehong
Retinal ischaemia-reperfusion (I/R) is a pathological process in many eye disorders. Neuroinflammation and cell pyroptosis have been recognized as important in the pathogenesis of tissue damage in retinal I/R. Interleukin (IL)-35 is a novel heterodimeric cytokine that exhibits anti-inflammatory activity in various autoimmune diseases, but its role in retinal I/R and the underlying molecular mechanisms remain unexplored. This research investigated the effect of IL-35 on retinal I/R and the inhibition of pyroptosis and neuronal death. In our study, a murine retinal I/R model was used to explore the neuroprotective effect of recombinant IL-35 protein in vivo. Primary murine microglial cells in pyroptosis and retinal ganglion cells (RGCs) in oxygen and glucose deprivation/reoxygenation (OGD/R) models were employed to assess the antipyroptotic and antiapoptotic effects of IL-35 in vitro. The data showed that IL-35 decreases retinal damage, RGC death, and inner plexiform layer (IPL) thinning in mice with retinal I/R injury, with significant attenuation of pyroptosis in the retina. The study also demonstrated the anti-pyroptotic action of IL-35 in primary microglia stimulated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP). Furthermore, primary RGC apoptosis induced by OGD/R was directly suppressed by IL-35, and IL-35-mediated neuroprotection was abrogated when miR-21 was blocked. In conclusion, our results suggest the mechanisms of RGC apoptosis and a new therapeutic target, IL-35, that exerts a robust neuroprotective effect against retinal I/R.
