Department of Ophthalmology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China; Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi Province, China.
Nanning Aier Eye Hospital, Aier Eye Hospital Group, China.
Exp Eye Res. 2022 Jun;219:109023. doi: 10.1016/j.exer.2022.109023. Epub 2022 Mar 8.
High myopia has been continually increasing globally until now and often results in visual impairment. Scleral extracellular matrix (ECM) remodeling is considered a common factor contributing to progression of myopia. However, the role of microRNAs (miRNAs) in regulating scleral ECM organization is not well understood. We aimed to explore the effect and regulatory mechanism of hsa-miR-142-3p on collagen I in human scleral fibroblasts in high myopia. First, next-generation sequencing was conducted to identify 37 miRNAs differentially expressed in the aqueous humor of high myopia samples and control samples. Furthermore, hsa-miR-142-3p in the aqueous humor was found to positively relate to the ocular axial length. Besides, the results of immunofluorescence and Western blot assay indicated that hsa-miR-142-3p overexpression decreased collagen I expression in the human fetal scleral fibroblasts (HFSFs); while hsa-miR-142-3p downregulation increased collagen I. Moreover, hsa-miR-142-3p targets TGFβ-1 gene expression. Quantitative polymerase chain reaction (qPCR) and Western blot analysis showed that miRNA 142-3p reduced TGFβ-1 expression while an inhibitor had an opposite effect. Therefore, there is an inverse relationship between changes in miR-142-3p expression levels and those of collagen1a1 in human scleral fibroblasts. Such a dependence suggests that miR-142-3p may be a target to improve therapeutic management of this condition.
高度近视在全球范围内一直在持续增加，并且经常导致视力损害。巩膜细胞外基质（ECM）重塑被认为是导致近视进展的共同因素。然而，miRNAs（miRNA）在调节巩膜 ECM 组织中的作用尚未得到很好的理解。我们旨在探讨 hsa-miR-142-3p 对高度近视患者人巩膜成纤维细胞中胶原 I 的影响及其调控机制。首先，通过下一代测序鉴定了高度近视样本和对照样本眼水中差异表达的 37 个 miRNA。此外，眼水中的 hsa-miR-142-3p 与眼球轴长呈正相关。此外，免疫荧光和 Western blot 检测结果表明，hsa-miR-142-3p 过表达降低了人胎儿巩膜成纤维细胞（HFSFs）中胶原 I 的表达；而 hsa-miR-142-3p 下调则增加了胶原 I 的表达。此外，hsa-miR-142-3p 靶向 TGFβ-1 基因表达。定量聚合酶链反应（qPCR）和 Western blot 分析表明，miRNA 142-3p 降低了 TGFβ-1 的表达，而抑制剂则有相反的作用。因此，人巩膜成纤维细胞中 miR-142-3p 表达水平的变化与胶原 1a1 的变化呈负相关。这种依赖性表明，miR-142-3p 可能是改善这种疾病治疗管理的靶点。
