Exosomal lncRNA-MIAT promotes neovascularization via the miR-133a-3p/MMP-X1 axis in diabetic retinopathy

Xinsheng Li; Qiuchen Cao; Changlin Xu; Jinfan Wang; Ting Pan; Qinghuai Liu; Ping Xie; Zizhong Hu

doi:10.1016/j.exer.2024.109912

Exosomal lncRNA-MIAT promotes neovascularization via the miR-133a-3p/MMP-X1 axis in diabetic retinopathy

Exp Eye Res. 2024 Apr 24:109912. doi: 10.1016/j.exer.2024.109912. Online ahead of print.

Authors

Xinsheng Li¹, Qiuchen Cao², Changlin Xu², Jinfan Wang², Ting Pan², Qinghuai Liu³, Ping Xie⁴, Zizhong Hu⁵

Affiliations

¹ Department of Ophthalmology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, jiangsu, China.
² Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, jiangsu, China.
³ Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, jiangsu, China. Electronic address: liuqh@njmu.edu.cn.
⁴ Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, jiangsu, China. Electronic address: Xieping9@126.com.
⁵ Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, jiangsu, China. Electronic address: huzizhong@njmu.edu.cn.

PMID: 38670210
DOI: 10.1016/j.exer.2024.109912

Abstract

Diabetic retinopathy (DR), a most common microangiopathy of diabetes, causes vision loss and even blindness. The mechanisms of exosomal lncRNA remain unclear in the development of DR. Here, we first identifed the pro-angiogenic effect of exosomes derived from vitreous humor of proliferative diabetic retinopathy patients, where lncRNA-MIAT was enriched inside. Secondly, lncRNA-MIAT was demonstrated significantly increased in exosomes from high glucose induced human retinal vascular endothelial cell, and can regulate tube formation, migration and proliferation ability to promote angiogenesis in vitro and in vivo. Mechanistically, the pro-angiogenic effect of lncRNA-MIAT was via the lncRNA-MIAT/miR-133a-3p/MMP-X1 axis. The reduced level of lncRNA-MIAT in this axis mitigated the generation of retinal neovascular in mouse model of oxygen-induced retinopathy (OIR), providing crucial evidence for lncRNA-MIAT as a potential clinical target. These findings enhance our understanding of the role of exosomal lncRNA-MIAT in retinal angiogenesis, and propose a promising therapeutic strategy against diabetic retinopathy.

Keywords: Angiogenesis; Diabetic retinopathy; Exosomes; LncRNA-MIAT; Vitreous humor.