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miR-1273h-5p 可保护人眼角膜上皮免受 UVR 诱导的氧化应激和凋亡:miR-1273h-5p 在气候性液滴状角膜病变中的作用。

miR-1273h-5p protects the human corneal epithelium against UVR-induced oxidative stress and apoptosis: Role of miR-1273h-5p in climatic droplet keratopathy.

机构信息

Department of Ophthalmology and the Eye Institute, Eye and Ear, Nose, and Throat Hospital, Fudan University, Shanghai, China; Key NHC Key Laboratory of Myopia (Fudan University), Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China.

Department of Ophthalmology and the Eye Institute, Eye and Ear, Nose, and Throat Hospital, Fudan University, Shanghai, China; Key NHC Key Laboratory of Myopia (Fudan University), Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China; Zhongshan Hospital, Fudan University, Shanghai, China.

出版信息

Exp Eye Res. 2023 Aug;233:109536. doi: 10.1016/j.exer.2023.109536. Epub 2023 Jun 17.

Abstract

Climatic droplet keratopathy (CDK) is characterized by an increased number of oil-like deposits on the most anterior corneal layers, which affect vision and can cause blindness. Environmental ultraviolet radiation (UVR) exposure is a major risk factor, but the underlying mechanism of CDK pathogenesis is unclear. Increasing evidence has demonstrated that miRNAs participate in the cross-talk with oxidative stress. We aimed to explore whether certain miRNAs are involved in the pathogenesis of CDK. We performed miRNA sequencing of tears from patients with CDK and healthy individuals from Tacheng region of Xinjiang and conducted bioinformatic analysis of key miRNAs. We also evaluated viability, migration, and apoptosis of human corneal epithelial cells (HCECs) subjected to UVR treatment. miR-1273h-5p expression was abnormally downregulated in the tears of patients with CDK. miR-1273h-5p promoted cell proliferation and migration and inhibited UVR-induced mitochondrial apoptosis. miR-1273h-5p protected HCECs against UVR-induced oxidative damage by reducing the accumulation of reactive oxygen species and inhibiting mitochondrial apoptosis via the activation of the Nrf2 pathway. Thus, our results suggest that miR-1273h-5p protects the corneal epithelium against UVR-induced oxidative stress damage.

摘要

气候性泪液点状角膜病变(CDK)的特征是在前角膜层上有大量油状沉积物,这会影响视力并导致失明。环境紫外线辐射(UVR)暴露是一个主要的危险因素,但 CDK 发病机制的潜在机制尚不清楚。越来越多的证据表明,miRNAs 参与与氧化应激的串扰。我们旨在探讨某些 miRNAs 是否参与 CDK 的发病机制。我们对来自新疆塔城地区 CDK 患者和健康个体的泪液进行了 miRNA 测序,并对关键 miRNAs 进行了生物信息学分析。我们还评估了暴露于 UVR 治疗的人角膜上皮细胞(HCEC)的活力、迁移和细胞凋亡。CDK 患者泪液中的 miR-1273h-5p 表达异常下调。miR-1273h-5p 通过减少活性氧物质的积累和抑制线粒体凋亡来激活 Nrf2 途径,从而促进细胞增殖和迁移,并抑制 UVR 诱导的线粒体凋亡。因此,我们的结果表明,miR-1273h-5p 可保护角膜上皮免受 UVR 诱导的氧化应激损伤。

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