氧化应激通过激活cGAS/STING通路介导角膜碱烧伤后视网膜损伤。

IF 3 2区 医学 Q1 OPHTHALMOLOGY Experimental eye research Pub Date : 2024-12-28 DOI:10.1016/j.exer.2024.110228
Keli Mao, Yanqiao Huang, Zheng Liu, Wenjun Sui, Chong Liu, Yujie Li, Jieting Zeng, Xiaobing Qian, Xinqi Ma, Xiaofeng Lin, Bingsheng Lou
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引用次数: 0

摘要

视网膜损伤是眼碱烧伤(OAB)后不可逆视力丧失的原因,但其潜在机制仍未被充分探讨。本文采用OAB小鼠模型,研究氧化应激(OS)对视网膜损伤的影响及其分子机制。结果显示碱损伤后视网膜OS增强。n -乙酰半胱氨酸(NAC)抗氧化治疗保留了视网膜结构,抑制细胞凋亡,减少视网膜炎症,证实了OS的作用。此外,增强的OS与线粒体功能障碍、mtDNA泄漏和细胞质dna传感信号的启动有关。然后确定了主要的DNA传感器环GMP-AMP合成酶(cGas)和干扰素基因cGas刺激因子(cGas /STING)途径的激活。值得注意的是,用C-176抑制cGAS/STING信号明显减少炎症和细胞凋亡,最终保护视网膜免受OAB。总的来说,我们的研究揭示了OS在oab诱导的视网膜损伤发生和cGAS/STING激活中的重要作用。此外,我们提供了使用抗氧化剂或STING抑制剂作为OAB后保护视网膜的潜在治疗方法的临床前验证。
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Oxidative stress mediates retinal damage after corneal alkali burn through the activation of the cGAS/STING pathway.

Retinal damage accounts for irreversible vision loss following ocular alkali burn (OAB), but the underlying mechanisms remain largely unexplored. Herein, using an OAB mouse model, we examined the impact of oxidative stress (OS) in retinal damage and its molecular mechanism. Results revealed that OS in the retina was enhanced soon after alkali injury. Antioxidant therapy with N-acetylcysteine (NAC) preserved the retinal structure, suppressed cell apoptosis and decreased retinal inflammation, confirming the role of OS. Moreover, enhanced OS was linked to mitochondrial dysfunction, mtDNA leakage and initiation of the cytosolic DNA-sensing signaling. The activation of the major DNA sensors cyclic GMP-AMP Synthase (cGas) and cGAS-Stimulator of Interferon Genes (cGAS/STING) pathway was then identified. Notably, inhibiting cGAS/STING signaling with C-176 markedly reduced inflammation and cell apoptosis and ultimately protected the retina against OAB. Overall, our study reveals the vital function of OS in the occurrence of OAB-induced retinal damage and the involvement of cGAS/STING activation. Furthermore, our provides preclinical validation of the use of an antioxidant or a STING inhibitor as a potential therapeutic approach to protect the retina after OAB.

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来源期刊
Experimental eye research
Experimental eye research 医学-眼科学
CiteScore
6.80
自引率
5.90%
发文量
323
审稿时长
66 days
期刊介绍: The primary goal of Experimental Eye Research is to publish original research papers on all aspects of experimental biology of the eye and ocular tissues that seek to define the mechanisms of normal function and/or disease. Studies of ocular tissues that encompass the disciplines of cell biology, developmental biology, genetics, molecular biology, physiology, biochemistry, biophysics, immunology or microbiology are most welcomed. Manuscripts that are purely clinical or in a surgical area of ophthalmology are not appropriate for submission to Experimental Eye Research and if received will be returned without review.
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