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一种选择性褪黑素 2 受体激动剂,IIK7,通过调节自噬和细胞凋亡过程来缓解蓝光诱导的角膜损伤。

A Selective Melatonin 2 Receptor Agonist, IIK7, Relieves Blue Light-Induced Corneal Damage by Modulating the Process of Autophagy and Apoptosis.

机构信息

Department of Ophthalmology, Chonnam National University Medical School, and Hospital, Gwangju 61469, Republic of Korea.

出版信息

Int J Mol Sci. 2024 Oct 19;25(20):11243. doi: 10.3390/ijms252011243.

DOI:10.3390/ijms252011243
PMID:39457025
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11508435/
Abstract

This study aims to investigate the effect of the selective MT2 receptor agonist, IIK7, on corneal autophagy and apoptosis, aiming to reduce corneal epithelial damage and inflammation from blue light exposure in mice. Eight-week-old C57BL/6 mice were divided into BL-exposed (BL) and BL-exposed with IIK7 treatment (BL + IIK7 group). Mice underwent blue light exposure (410 nm, 100 J) twice daily with assessments at baseline and on days 3, 7, and 14. Corneal samples were analyzed for MT2 receptor expression, autophagy markers (LC3-II and p62), and apoptosis indicators (BAX expression and TUNEL assay). Then, mice were assigned to normal control, BL, and BL + IIK7. Ocular surface parameters, including corneal fluorescein staining scores, tear volume, and tear film break-up time, were evaluated on days 7 and 14. On day 14, reactive oxygen species (ROS) levels and CD4 IFN-γ T cells percentages were measured. The BL group exhibited higher LC3-II and p62 expression, while the BL + IIK7 group showed reduced expression ( < 0.05). The TUNEL assay showed reduced apoptosis in the BL + IIK7 group compared to the BL group. ROS levels were lower in the BL + IIK7 group. The BL + IIK7 group showed improved ocular surface parameters, including decreased corneal fluorescein staining and increased tear volume. The percentages of CD4 IFN-γ T cells indicated reduced inflammatory responses in the BL + IIK7 group. The MT2 receptor agonist IIK7 regulates corneal autophagy and apoptosis, reducing corneal epithelial damage and inflammation from blue light exposure.

摘要

本研究旨在探讨选择性 MT2 受体激动剂 IIK7 对角膜自噬和凋亡的影响,以期减轻蓝光照射诱导的小鼠角膜上皮损伤和炎症。将 8 周龄 C57BL/6 小鼠分为暴露于蓝光(BL)和暴露于蓝光同时给予 IIK7 处理(BL + IIK7 组)的两组。小鼠每日接受两次蓝光照射(410nm,100J),分别于基线和第 3、7、14 天进行评估。分析角膜 MT2 受体表达、自噬标志物(LC3-II 和 p62)和凋亡指标(BAX 表达和 TUNEL 检测)。然后,将小鼠分为正常对照组、BL 组和 BL + IIK7 组。于第 7、14 天评估眼表参数,包括角膜荧光素染色评分、泪液体积和泪膜破裂时间。于第 14 天测量活性氧(ROS)水平和 CD4 IFN-γ T 细胞百分比。BL 组 LC3-II 和 p62 表达升高,而 BL + IIK7 组表达降低(<0.05)。TUNEL 检测显示 BL + IIK7 组较 BL 组凋亡减少。BL + IIK7 组 ROS 水平降低。BL + IIK7 组眼表参数改善,包括角膜荧光素染色评分降低和泪液体积增加。CD4 IFN-γ T 细胞百分比表明 BL + IIK7 组炎症反应减轻。MT2 受体激动剂 IIK7 调节角膜自噬和凋亡,减轻蓝光照射诱导的角膜上皮损伤和炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c791/11508435/6aa419a108d8/ijms-25-11243-g006.jpg
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