Liu Shenghua, Yi Jinping, Lu Shiyao, Cao Jiamin, Xie Bingyu, Tan Yao, Xiong Wei
Department of Ophthalmology, The Third Xiangya Hospital, Central South University, Yuelu District, Changsha, Hunan, People's Republic of China.
Invest Ophthalmol Vis Sci. 2025 Jul 1;66(9):41. doi: 10.1167/iovs.66.9.41.
Thyroid eye disease (TED) is an autoimmune condition of the orbit characterized by significant morbidity. MicroRNAs (miRNAs) have been identified as key modulators of immune responses and fibrotic processes, with miR-320a emerging as a potential modulator in TED pathogenesis.
This study investigated miR-320a's role in TED by analyzing its expression in TED tissues and assessing the impact of its inhibition on fibroblast activation, fibrosis, and oxidative stress. Peroxiredoxin 3 (PRDX3) was identified as a direct target of miR-320a, and its functional consequences were evaluated. In vivo experiments were also conducted to validate the findings.
Inhibition of miR-320a reduced fibroblast activation, fibrosis, and oxidative stress markers. PRDX3 knockdown amplified these effects, indicating its importance in miR-320a-mediated pathways. Overexpression of miR-320a further promoted fibroblast activation, as evidenced by decreased cell viability, DNA synthesis, and the expression levels of fibrotic markers. PRDX3 overexpression could also notably eliminate the effects of miR-320a overexpression. In vivo targeting of the miR-320a/PRDX3 axis reduced oxidative stress and fibrosis in TED models.
The study highlights the critical role of miR-320a in TED pathogenesis through its regulation of orbital fibroblast (OF) activation, fibrosis, oxidative stress, and the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway, mediated by its interaction with PRDX3. Targeting the miR-320a/PRDX3 axis represents a promising therapeutic strategy to alleviate the oxidative stress and fibrotic alterations in TED, underscoring the potential of miR-320a as a therapeutic target in managing TED progression.
甲状腺眼病（TED）是一种眼眶自身免疫性疾病，具有较高的发病率。微小RNA（miRNA）已被确定为免疫反应和纤维化过程的关键调节因子，miR-320a在TED发病机制中成为一种潜在的调节因子。
本研究通过分析miR-320a在TED组织中的表达，并评估其抑制对成纤维细胞活化、纤维化和氧化应激的影响，来研究miR-320a在TED中的作用。过氧化物酶3（PRDX3）被确定为miR-320a的直接靶点，并对其功能后果进行了评估。还进行了体内实验以验证这些发现。
抑制miR-320a可降低成纤维细胞活化、纤维化和氧化应激标志物。敲低PRDX3可放大这些效应，表明其在miR-320a介导的途径中的重要性。miR-320a的过表达进一步促进了成纤维细胞活化，细胞活力、DNA合成以及纤维化标志物的表达水平降低证明了这一点。PRDX3的过表达也可显著消除miR-320a过表达的影响。在体内靶向miR-320a/PRDX3轴可降低TED模型中的氧化应激和纤维化。
该研究强调了miR-320a在TED发病机制中的关键作用，它通过与PRDX3相互作用调节眼眶成纤维细胞（OF）活化、纤维化、氧化应激以及p38丝裂原活化蛋白激酶（p38 MAPK）信号通路。靶向miR-320a/PRDX3轴是减轻TED氧化应激和纤维化改变的一种有前景的治疗策略，强调了miR-320a作为控制TED进展的治疗靶点的潜力。
