Tianjin International Joint Research and Development Center of Ophthalmology and Vision Science, Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, No. 251, Fukang Road, Nankai District, Tianjin, 300384, China.
The Second Hospital of Tianjin Medical University, 23 Pingjiang Road, Hexi District, Tianjin, 300211, China.
Int J Biochem Cell Biol. 2021 Jun;135:105975. doi: 10.1016/j.biocel.2021.105975. Epub 2021 Apr 7.
Early diagnosis and precise monitoring of the development of proliferative diabetic retinopathy (PDR) can significantly improve therapeutic strategies and help decrease blindness caused by it. Extracellular vesicles (EVs) were recently found to be involved in intercellular communications and are a potential source for the discovery of novel biomarkers. The current study aims to investigate the effectiveness of microRNAs (miRNAs) encapsulated in small EVs (sEVs) as minimally invasive biomarkers for PDR. SEVs were extracted from plasma of healthy subjects, diabetic patients, nonPDR patients and PDR patients. Then, we performed microarray analysis to determine the miRNA expression profile. MiR-431-5p expression doubled in the PDR patients compared with the healthy controls and the diabetic patients. We further found that miR-431-5p expression was 2.3 times higher in 4-hydroxynonenal treated human retinal capillary endothelial cells (HRCECs) than the control. After transfection with miR-431-5p mimics, proliferation of HRCECs was promoted, while transfection with miR-431-5p inhibitor demonstrated the opposite effect. The present findings indicate that circulating sEVs showed a differential miRNA profile in PDR patients. MiR-431-5p was involved in the pathogenesis of PDR development and may function as a novel biomarker for PDR.
早期诊断和精确监测增殖性糖尿病视网膜病变（PDR）的发展，可以显著改善治疗策略，并有助于减少由其引起的失明。最近发现细胞外囊泡（EVs）参与细胞间通讯，是发现新型生物标志物的潜在来源。本研究旨在探讨包裹在小细胞外囊泡（sEVs）中的微小 RNA（miRNAs）作为 PDR 微创生物标志物的有效性。从小鼠、糖尿病患者、非 PDR 患者和 PDR 患者的血浆中提取 sEVs。然后，我们进行了微阵列分析以确定 miRNA 的表达谱。与健康对照组和糖尿病组相比，PDR 患者的 miR-431-5p 表达增加了一倍。我们还发现，4-羟基壬烯醛处理的人视网膜毛细血管内皮细胞（HRCECs）中的 miR-431-5p 表达比对照组高 2.3 倍。转染 miR-431-5p 模拟物后，HRCEC 的增殖得到促进，而转染 miR-431-5p 抑制剂则表现出相反的效果。这些发现表明，PDR 患者的循环 sEVs 显示出不同的 miRNA 图谱。miR-431-5p 参与 PDR 发展的发病机制，可能作为 PDR 的新型生物标志物。
