IL-17A enhances the inflammatory response of glaucoma through Act1/ TRAF6/NF-κB pathway

作者全名：Zheng, Yunfan; Mou, Zhenni; Tan, Sisi; Wang, Xiaochen; Yuan, Jingchang; Li, Hong

作者地址：[Zheng, Yunfan; Mou, Zhenni; Tan, Sisi; Wang, Xiaochen; Yuan, Jingchang; Li, Hong] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Eye Inst, Chongqing Branch,Municipal Div,Natl Clin Res Ctr O, Chongqing, Peoples R China

通信作者：Li, H (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Chongqing Eye Inst, Chongqing Branch,Municipal Div,Natl Clin Res Ctr O, Chongqing, Peoples R China.

来源：NEUROCHEMISTRY INTERNATIONAL

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001255592500001

JCR分区：Q1

影响因子：4.4

年份：2024

卷号：178

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Glaucoma; IL-17A; IL-17A neutralizing antibody; NF-kappa B

摘要：Objectives: To investigate the possible roles of Interleukin 17A (IL-17A) and IL-17A neutralizing antibodies (IL17Ab) in glaucoma and the potential mechanisms. Methods: The two glaucoma animal models, chronic ocular hypertension (COH) and N-methyl-D-aspartate (NMDA)-induced retinal ganglion cell (RGC) damage, were established and treated with intravitreal injection of IL-17A or IL-17Ab. Intraocular pressure (IOP) was measured by a rebound tonometer. The retina and RGC injury were evaluated by HE staining, TUNLE assay and Brn3a immunofluorescence staining. The frequency of IL17A+CD4+T cells in peripheral blood was detected by flow cytometry. The expression of glial fibrillary acidic protein (GFAP) was detected by immunofluorescence staining, Western Blot and qPCR in retina. The RNA and protein expression of Act1/TRAF6/NF-kappa B were detected by Western Blot and qPCR in retina. Results: The expression of IL-17A increased in glaucoma models. After intravitreal injection of IL-17A, in the retina, the number of RGCs decreased, the apoptosis of RGCs increased, the M & uuml;ller cell gliosis was more obvious. In addition, peripheral inflammation aggravated. Whereas the intravitreal injection of IL-17Ab alleviated the relevant manifestations and peripheral inflammation, reduced the gliosis of M & uuml;ller cells. In the COH model, IOP increased after the injection of IL-17A, while the intravitreal injection of IL-17Ab led to a decrease in IOP. Furthermore, IL-17A promotes the apoptosis of RGCs by binding to IL-17A receptor, activating Act1/TRAF6/NF kappa B pathways. Conclusion: IL-17A plays a role in and aggravates RGC damage in glaucoma. IL-17Ab can neutralize the proinflammatory effect of IL-17A and have a protective function in glaucoma. These findings reveal the importance of IL-17A in the pathogenesis of glaucoma, which will shed light on a novel direction for the prevention and treatment of glaucoma, and also provide a reference for further research on other retinal diseases.

基金机构：National Natural Science Foundation of China [81974131]

基金资助正文：<BOLD>Funding</BOLD> This work was supported by National Natural Science Foundation of China (Grant nos. 81974131) .