Lv Lingfeng, Shao Qing, Zhou Jibo, Zhu Yi
Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Aier Eye Hospital, Shanghai, China; Shanghai Aier Eye Institute, Shanghai, China.
Exp Eye Res. 2025 Sep;258:110474. doi: 10.1016/j.exer.2025.110474. Epub 2025 Jun 4.
Myopia, especially high myopia, is a global health concern with a rising prevalence, yet its underlying mechanisms remain incompletely understood. MicroRNAs (miRNAs) have been implicated in the pathogenesis of myopia, potentially playing a critical role in its development. This study aimed to investigate the mechanism by which miR-29a mediates scleral remodelling through the activation of Toll-like receptors (TLRs). By using a form-deprivation myopia (FDM) guinea pig model, we combined fluorescence in situ hybridization (FISH) and qPCR to demonstrate that the expression of miR-29a and inflammatory cytokines (TNF-α and IL-6) was significantly upregulated in the sclera of myopic eyes, whereas TLR7/8 expression remained unchanged. In human scleral fibroblasts (HSFs), FISH and RNA immunoprecipitation (RIP) assays revealed that miR-29a directly interacts with TLR7 and TLR8, forming ligand‒receptor complexes. This interaction activated downstream inflammatory signalling, leading to upregulated expression of proinflammatory cytokines (TNF-α and IL-6), downregulated expression of anti-inflammatory IL-10, and suppression of COL1A1 expression. Inhibition of TLR7/8 signalling reversed these effects, restoring COL1A1 levels and attenuating inflammatory responses. Our findings reveal a novel mechanism by which miR-29a promotes scleral remodelling through TLR7/8-mediated inflammatory signalling, providing new insights into the pathogenesis of myopia and potential therapeutic targets for its prevention and treatment.
近视，尤其是高度近视，是一个全球关注的健康问题，其患病率不断上升，但其潜在机制仍未完全明了。微小RNA（miRNA）已被认为与近视的发病机制有关，可能在其发展中起关键作用。本研究旨在探讨miR-29a通过激活Toll样受体（TLR）介导巩膜重塑的机制。通过使用形觉剥夺性近视（FDM）豚鼠模型，我们结合荧光原位杂交（FISH）和定量聚合酶链反应（qPCR）来证明，miR-29a和炎性细胞因子（肿瘤坏死因子-α和白细胞介素-6）在近视眼中的巩膜中表达显著上调，而TLR7/8的表达保持不变。在人巩膜成纤维细胞（HSF）中，FISH和RNA免疫沉淀（RIP）分析显示，miR-29a直接与TLR7和TLR8相互作用，形成配体-受体复合物。这种相互作用激活下游炎性信号传导，导致促炎细胞因子（肿瘤坏死因子-α和白细胞介素-6）表达上调，抗炎性白细胞介素-10表达下调，并抑制COL1A1表达。抑制TLR7/8信号传导可逆转这些效应，恢复COL1A1水平并减轻炎症反应。我们的研究结果揭示了一种新的机制，即miR-29a通过TLR7/8介导的炎性信号传导促进巩膜重塑，为近视的发病机制以及预防和治疗的潜在治疗靶点提供了新的见解。
