MicroRNA-93/STAT3 signalling pathway mediates retinal microglial activation and protects retinal ganglion cells in an acute ocular hypertension model.
MicroRNA-93/STAT3 signalling pathway mediates retinal microglial activation and protects retinal ganglion cells in an acute ocular hypertension model.
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DOI：
10.1038/s41419-020-03337-5
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发表时间：
2021-01-04
影响因子：
9
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Wang Y;Chen S;Wang J;Liu Y;Chen Y;Wen T;Fang X;Vidal-Sanz M;Jonas JB;Zhang X
青光眼是一种常见的神经退行性疾病，也是世界范围内不可逆性失明的主要原因。视网膜小胶质细胞介导的神经炎症参与了视神经损伤的过程，但驱动这种小胶质细胞活化的机制仍然是难以捉摸的。先前的研究报道microRNA与视网膜小胶质细胞反应和神经细胞凋亡有关。在本研究中，我们发现microRNA-93- 5 p（miR-93）在体内和体外视网膜小胶质细胞的反应中起关键作用。与对照组相比，大鼠急性高眼压（AOH）模型的视网膜中miR-93水平显著降低，该模型伴有视网膜小胶质细胞活化、炎性细胞因子过度产生和随后的视网膜神经节细胞（RGC）死亡。诱导miR-93过表达显著降低小胶质细胞增殖、迁移和细胞因子释放，抑制靶基因信号转导子和转录激活子3（STAT 3）和p-STAT 3的表达，并与减少RGC损失相关。用STAT 3抑制剂治疗也降低了AOH损伤后视网膜小胶质细胞的活化。综上所述，这些结果表明miR-93/STAT 3通路与视网膜小胶质细胞介导的神经炎症的下调直接相关，并显示出神经保护作用。通过miR-93调节小胶质细胞活化可作为病理性高眼压神经保护治疗的靶点。
Glaucoma is a common neurodegenerative disease and a leading cause of irreversible blindness worldwide. Retinal microglia-mediated neuroinflammation is involved in the process of optic nerve damage, but the mechanisms driving this microglial activation remain mostly elusive. Previous investigations reported that microRNAs are associated with the retinal microglial reaction and neural apoptosis. In the present study, we found that microRNA-93-5p (miR-93) played a key role in the reaction of retinal microglial cells in vivo and in vitro. The miR-93 level was significantly reduced in the retinae of rat acute ocular hypertension (AOH) models, which were accompanied by retinal microglial activation, overproduction of inflammatory cytokines, and subsequent retinal ganglion cells (RGCs) death, versus the retinae of controls. The induction of miR-93 overexpression significantly reduced microglial proliferation, migration and cytokine release, inhibited the expression of the target gene signal transducer and activator of transcription 3 (STAT3) and p-STAT3, and was associated with a reduced loss of RGCs. Treatment with a STAT3 inhibitor also decreased retinal microglial activation after AOH injury. Taken together, these results suggest that the miR-93/STAT3 pathway is directly related to the downregulation of retinal microglia-mediated neuro-inflammation and showed a neuroprotective effect. Regulating microglial activation through miR-93 may serve as a target for neuroprotective therapy in pathological ocular hypertension.
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影响因子：
3.7
作者：
Sticht C;De La Torre C;Parveen A;Gretz N
通讯作者：
Gretz N
影响因子：
4.7
作者：
Przanowski, Piotr;Dabrowski, Michal;Ellert-Miklaszewska, Aleksandra;Kloss, Michal;Mieczkowski, Jakub;Kaza, Beata;Ronowicz, Anna;Hu, Feng;Piotrowski, Arkadiusz;Kettenmann, Helmut;Komorowski, Jan;Kaminska, Bozena
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Kaminska, Bozena
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影响因子：
4.4
作者：
Liu, Yaoming;Chen, Yang;Zhang, Xiulan
通讯作者：
Zhang, Xiulan
影响因子：
4.4
作者：
Chen, Shida;Zhang, Xiulan
通讯作者：
Zhang, Xiulan
影响因子：
3.4
作者：
Huang, Tzu Lun;Chang, Chung Hsing;Tsai, Rong Kung
通讯作者：
Tsai, Rong Kung