M2 macrophage-derived extracellular vesicles ameliorate Benzalkonium Chloride-induced dry eye

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research Pub Date : 2024-08-13 DOI:10.1016/j.exer.2024.110041

Chao Yang , Qi Gao , Jing Liu , Yan Wu , Xufeng Hou , Lijuan Sun , Xuhui Zhang , Yao Lu , Yingxin Yang

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Abstract

Dry eye disease (DED) is a common ocular condition affecting a significant portion of the global population, yet effective treatment options remain elusive. This study investigates the therapeutic potential of M2 macrophage-derived extracellular vesicles (M2-EVs) in a mouse model of DED. The DED model was established using 0.2% benzalkonium chloride (BAC) eye drops, applied twice daily for a week. Post induction, the mice were categorized into 5 groups: PBS, Sodium Hyaluronate (HA, 0.1%), Fluoromethalone (FM, 0.1%), M0-EVs, and M2-EVs. The efficacy of M2-EVs was assessed through tear production, corneal fluorescein staining and HE staining. RNA sequencing (RNA-seq) was employed to investigate the mechanisms underlying the therapeutic effects of M2-EVs in DED. Notably, the M2-EVs treated group exhibited the highest tear secretion, indicating improved tear film stability and reduced corneal surface damage. Histological analysis revealed better corneal structure organization in the M2-EVs group, suggesting enhanced ocular surface repair and corneal preservation. Furthermore, M2-EVs treatment significantly decreased pro-inflammatory cytokine levels and showed unique enrichment of genes related to retinal development. These findings suggest that M2-EVs could serve as a promising noninvasive therapeutic approach for human DED, targeting ocular surface inflammation.

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M2 巨噬细胞衍生的细胞外囊泡可改善苯扎氯铵诱发的干眼症。

干眼症（DED）是一种常见的眼部疾病，影响着全球相当一部分人口，但有效的治疗方案却仍然乏善可陈。本研究调查了 M2 巨噬细胞衍生的细胞外囊泡（M2-EVs）在小鼠 DED 模型中的治疗潜力。DED 模型使用 0.2% 苯扎氯铵（BAC）滴眼液建立，每天滴用两次，持续一周。诱导后，小鼠被分为 5 组：PBS组、透明质酸钠组（HA，0.1%）、氟甲酮组（FM，0.1%）、M0-EV组和M2-EV组。通过泪液分泌、角膜荧光素染色和 HE 染色来评估 M2-EVs 的疗效。RNA测序（RNA-seq）被用来研究M2-EVs对DED治疗效果的机制。值得注意的是，M2-EVs治疗组的泪液分泌量最高，表明泪膜稳定性得到改善，角膜表面损伤减少。组织学分析显示，M2-EVs 治疗组的角膜结构组织更好，表明眼表修复和角膜保存能力增强。此外，M2-EVs 治疗显著降低了促炎细胞因子水平，并显示出与视网膜发育相关基因的独特富集。这些研究结果表明，M2-EVs可以作为一种针对眼表炎症的非侵入性治疗方法，用于治疗人类DED。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

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.