Tumor Necrosis Factor Alpha-Mediated Interaction Between Microglia and Müller Cells Exacerbates Retinal Ganglion Cell Damage in Experimental Glaucoma.

IF 5.8 2区医学 Q1 NEUROSCIENCES

Neuroscience bulletin Pub Date : 2025-08-30 DOI:10.1007/s12264-025-01478-1

Shu-Ying Li, Hong Zhou, Guoli Zhao, Wen-Wen Ding, Yu Zhang, Yong-Chen Wang, Fang Li, Yanying Miao, Xing-Huai Sun, Zhongfeng Wang

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引用次数: 0

Abstract

Interaction between Müller cells and microglia aggravates neuroinflammation, resulting in retinal ganglion cell (RGC) death in glaucoma. Here, we investigated how tumor necrosis factor-alpha (TNF-α) produced by activated microglia mediates the crosstalk between Müller cells and microglia and impacts RGC injury in a chronic ocular hypertension (COH) glaucoma model. In COH retinas, elevated TNF-α induced the activation of Müller cells and microglia, and recruited microglia to the ganglion cell layer. Co-culture with Müller cells enhanced TNF-α-induced microglial activation, migration, and proliferation. Both in vivo and in vitro experiments confirmed that chemokine C-C motif ligand 2 (CCL2), primarily released from Müller cells, mediated the TNF-α-induced effects on microglia in COH retinas. Knockdown of CCL2 attenuated RGC damage and vision loss. Our results demonstrate that TNF-α released from microglia induces the secretion of CCL2 from Müller cells, thus inducing microglial activation and migration, exacerbating retinal neuroinflammation and RGC injury in glaucoma.

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实验性青光眼中肿瘤坏死因子α介导的小胶质细胞和勒细胞之间的相互作用加剧了视网膜神经节细胞的损伤。

青光眼患者视网膜神经节细胞（RGC）的死亡，是青光眼患者视网膜神经节细胞与小胶质细胞相互作用的结果。在此，我们研究了激活的小胶质细胞产生的肿瘤坏死因子-α (TNF-α)如何介导 ller细胞和小胶质细胞之间的相互作用，并影响慢性高眼压（COH）青光眼模型的RGC损伤。在COH视网膜中，升高的TNF-α诱导 ller细胞和小胶质细胞的活化，并将小胶质细胞募集到神经节细胞层。与m ller细胞共培养可增强TNF-α-诱导的小胶质细胞活化、迁移和增殖。体内和体外实验均证实，趋化因子C-C基序配体2 （CCL2）主要来自于 ller细胞，可介导TNF-α-对COH视网膜小胶质细胞的影响。CCL2的敲除减轻了RGC损伤和视力丧失。我们的研究结果表明，小胶质细胞释放的TNF-α诱导 ller细胞分泌CCL2，从而诱导小胶质细胞活化和迁移，加重青光眼视网膜神经炎症和RGC损伤。

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来源期刊

Neuroscience bulletin NEUROSCIENCES-

CiteScore

7.20

自引率

16.10%

发文量

163

审稿时长

6-12 weeks

期刊介绍： Neuroscience Bulletin (NB), the official journal of the Chinese Neuroscience Society, is published monthly by Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) and Springer. NB aims to publish research advances in the field of neuroscience and promote exchange of scientific ideas within the community. The journal publishes original papers on various topics in neuroscience and focuses on potential disease implications on the nervous system. NB welcomes research contributions on molecular, cellular, or developmental neuroscience using multidisciplinary approaches and functional strategies. We feature full-length original articles, reviews, methods, letters to the editor, insights, and research highlights. As the official journal of the Chinese Neuroscience Society, which currently has more than 12,000 members in China, NB is devoted to facilitating communications between Chinese neuroscientists and their international colleagues. The journal is recognized as the most influential publication in neuroscience research in China.