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泪液炎症细胞因子作为近视性黄斑变性的潜在生物标志物

Tear inflammatory cytokines as potential biomarkers for myopic macular degeneration.

作者信息

Guo Dongling, Qi Jiao, Du Yu, Zhao Chen, Liu Shuyu, Lu Yi, Zhu Xiangjia

机构信息

Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Myopia, Fudan University, Shanghai, China; Key Laboratory of Myopia, Chinese Academy of Medical Science, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China.

Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China.

出版信息

Exp Eye Res. 2023 Oct;235:109648. doi: 10.1016/j.exer.2023.109648. Epub 2023 Sep 11.

Abstract

Previous studies have reported that inflammatory cytokine levels increase in the intraocular fluids (aqueous humor and vitreous) of highly myopic eyes, However, there has been currently no study revealing the levels of inflammatory cytokines in tear. Therefore, this study aimed to determine tear cytokine levels of highly myopic eyes, and their relationships with myopic macular degeneration (MMD). This case-control study screened inflammatory cytokines of tear samples from 132 highly myopic and 105 emmetropic eyes using a multiplex cytokine antibody array, and cytokines showing significant intergroup differences were further validated using ProQuantum immunoassays in tear samples from another 60 highly myopic and 60 emmetropic eyes. Ultra-widefield fundus photographs of eyes were classified according to the meta-analyses of the Pathologic Myopia Classification. Associations between tear cytokine levels and MMD category were investigated. As a result, tear levels of interleukin (IL)-6, IL-13 and monocyte chemoattractant protein (MCP)-1 were screened significantly higher in highly myopic eyes than in emmetropic controls (IL-6: 11.70 ± 16.81 versus 8.22 ± 10.76 pg/mL; MCP-1: 63.60 ± 54.40 versus 33.87 ± 43.82 pg/mL; both P < 0.05). Validation assays further demonstrated the elevated concentrations of IL-6 and MCP-1 (IL-6: 13.97 ± 8.41 versus 8.06 ± 7.94 pg/mL, P < 0.001; MCP-1: 32.69 ± 8.41 versus 18.07 ± 8.41 pg/mL, P = 0.003). Tear levels of IL-6 and MCP-1 differed significantly among MMD categories (both P < 0.05). The area under receiver operating characteristic curve were 0.783 and 0.682 respectively (both P < 0.05), when using tear IL-6 and MCP-1 levels to predict the presence of MMD (category ≥2). The ordered logistic regression model also indicated that longer axial length, and higher IL-6 and MCP-1 tear levels were independent predictors of higher MMD category. In our study, highly myopic eyes presented significantly higher levels of tear IL-6 and MCP-1, which may also serve as potential biomarkers for MMD.

摘要

先前的研究报道,高度近视眼的眼内液(房水和玻璃体)中炎症细胞因子水平会升高。然而,目前尚无研究揭示泪液中炎症细胞因子的水平。因此,本研究旨在测定高度近视眼的泪液细胞因子水平及其与近视性黄斑变性(MMD)的关系。这项病例对照研究使用多重细胞因子抗体阵列筛选了132只高度近视眼和105只正视眼的泪液样本中的炎症细胞因子,对于组间差异显著的细胞因子,在另外60只高度近视眼和60只正视眼的泪液样本中使用ProQuantum免疫测定法进行了进一步验证。根据病理性近视分类的荟萃分析对眼睛的超广角眼底照片进行分类。研究了泪液细胞因子水平与MMD类别之间的关联。结果显示,高度近视眼的泪液中白细胞介素(IL)-6、IL-13和单核细胞趋化蛋白(MCP)-1水平显著高于正视对照组(IL-6:11.70±16.81对8.22±10.76 pg/mL;MCP-1:63.60±54.40对33.87±43.82 pg/mL;均P<0.05)。验证试验进一步证实了IL-6和MCP-1浓度升高(IL-6:13.97±8.41对8.06±7.94 pg/mL,P<0.001;MCP-1:32.69±8.41对18.07±8.41 pg/mL,P=0.003)。IL-6和MCP-1的泪液水平在不同MMD类别之间存在显著差异(均P<0.05)。当使用泪液IL-6和MCP-1水平预测MMD(类别≥2)的存在时,受试者工作特征曲线下面积分别为0.783和0.682(均P<0.05)。有序逻辑回归模型还表明,眼轴长度更长以及泪液中IL-6和MCP-1水平更高是MMD类别更高的独立预测因素。在我们的研究中,高度近视眼的泪液IL-6和MCP-1水平显著更高,它们也可能作为MMD的潜在生物标志物。

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