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眼内炎症因子水平升高与近视性视网膜病变中的视网膜血管和神经退行性变有关。

Higher Intraocular Levels of Inflammatory Factors are Related to Retinal Vascular and Neurodegeneration in Myopic Retinopathy.

作者信息

Zeng Ling, Yang Zhikuan, Pan Wei, Lin Ding, Tang Yao, Chen Baihua, Xu Heping, Li Xiaoning

机构信息

Aier Academy of Ophthalmology, Central South University, Changsha, People's Republic of China.

Changsha Aier Eye Hospital, Changsha, People's Republic of China.

出版信息

J Inflamm Res. 2024 Dec 11;17:10889-10900. doi: 10.2147/JIR.S484338. eCollection 2024.

Abstract

PURPOSE

In this study, we aimed to investigate the relationship between the intraocular levels of inflammatory factors and myopia-related retinal vascular and neuronal degeneration.

PATIENTS AND METHODS

One hundred and forty-seven patients with Implantable Collamer Lens (ICL) implantation were enrolled and all participants received comprehensive ophthalmic examination. About 100~150 ul of aqueous humor was collected immediately before ICL surgery. The levels of inflammatory factors including Aggrecan, April, BAFF, CCL5, CD163, Chi3l1, gp130, IL-6Rα, IL-8, IL-10, IL-11, IL-12, IL-19, IL-27, IL-28A, IL-34, IFN-β, IFN-γ, MMP-1, MMP-2, MMP-3 and PTX3 in the aqueous humor were measured using the Luminex Multiplexing system.

RESULTS

Results showed that aqueous humor levels of pro-inflammatory factors Chi3l1, IL-6Rα, IL-8, IL-12, IL-27, inflammation-related cytokines April, BAFF and IL-34 progressively increased from the progression of myopic retinopathy. Conversely, the aqueous levels of IL-11 and Aggrecan gradually decreased from the progression of myopic retinopathy. Correlation analysis showed that the intraocular levels of Chi3l1, IL-6Rα, IL-8, IL-27 and BAFF were negatively correlated with retinal vascular density. The intraocular level of IL-6Rα was negatively correlated with retinal neuronal thickness. Protein-Protein Interaction (PPI) analysis revealed that Chi3l1 and Aggrecan were the upstream cytokines that affect IL-10 and IL-8 in the pathological myopic eyes. KEGG pathway analysis showed that cytokine-cytokine receptor interaction, JAK-STAT signaling pathway, rheumatoid arthritis, and chagas disease were influenced by these altered inflammatory factors (adjusted p-value<0.001).

CONCLUSION

The production of inflammatory factors in the eyes of individuals with high myopia and pathological myopia was altered, and the elevated levels of intraocular pro-inflammatory factors such as Chi3l1, IL-6Rα, and IL-8 were closely associated with myopia-related retinal microvascular and neurodegeneration.

摘要

目的

在本研究中,我们旨在探究眼内炎症因子水平与近视相关视网膜血管及神经元变性之间的关系。

患者与方法

招募了147例接受可植入式胶原晶状体(ICL)植入术的患者,所有参与者均接受了全面的眼科检查。在ICL手术前立即采集约100~150微升房水。使用Luminex多重检测系统测量房水中包括聚集蛋白聚糖、增殖诱导配体(APRIL)、B淋巴细胞激活因子(BAFF)、趋化因子配体5(CCL5)、CD163、几丁质酶3样蛋白1(Chi3l1)、糖蛋白130(gp130)、白细胞介素6受体α(IL-6Rα)、白细胞介素8(IL-8)、白细胞介素10(IL-10)、白细胞介素11(IL-11)、白细胞介素12(IL-12)、白细胞介素19(IL-19)、白细胞介素27(IL-27)、白细胞介素28A(IL-28A)、白细胞介素34(IL-34)、干扰素-β(IFN-β)、干扰素-γ(IFN-γ)、基质金属蛋白酶1(MMP-1)、基质金属蛋白酶2(MMP-2)、基质金属蛋白酶3(MMP-3)和五聚素3(PTX3)等炎症因子的水平。

结果

结果显示,促炎因子Chi3l1、IL-6Rα、IL-8、IL-12、IL-27以及炎症相关细胞因子APRIL、BAFF和IL-34的房水水平随着近视性视网膜病变的进展而逐渐升高。相反,IL-11和聚集蛋白聚糖的房水水平随着近视性视网膜病变的进展而逐渐降低。相关性分析表明,Chi3l1、IL-6Rα、IL-8、IL-27和BAFF的眼内水平与视网膜血管密度呈负相关。IL-6Rα的眼内水平与视网膜神经元厚度呈负相关。蛋白质-蛋白质相互作用(PPI)分析显示,Chi3l1和聚集蛋白聚糖是在病理性近视眼中影响IL-10和IL-8的上游细胞因子。京都基因与基因组百科全书(KEGG)通路分析表明,细胞因子-细胞因子受体相互作用、JAK-STAT信号通路、类风湿关节炎和恰加斯病受到这些改变的炎症因子的影响(校正P值<0.001)。

结论

高度近视和病理性近视患者眼内炎症因子的产生发生了改变,眼内促炎因子如Chi3l1、IL-6Rα和IL-8水平的升高与近视相关的视网膜微血管和神经变性密切相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52e7/11646394/daa2e47bb007/JIR-17-10889-g0001.jpg

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