Asakage Masaki, Usui Yoshihiko, Komatsu Hiroyuki, Maruyama Kazuichi, Nezu Naoya, Shimizu Hiroyuki, Tsubota Kinya, Yamakawa Naoyuki, Umezu Tomohiro, Takanashi Masakatsu, Kuroda Masahiko, Goto Hiroshi
Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishi-Shinjuku, Shinjuku-Ku, Tokyo, 160-0023, Japan.
Department of Vision Informatics, Graduate School of Medicine, Osaka University, 22 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Graefes Arch Clin Exp Ophthalmol. 2025 Feb;263(2):501-526. doi: 10.1007/s00417-024-06619-2. Epub 2024 Sep 9.
MicroRNAs (miRNAs) are non-coding RNAs which have attracted attention as biomarkers in a variety of diseases. However, extensive unbiased analysis of miRNA in vitreous humor of sarcoidosis patients has not been reported. In the present study, we comprehensively analyzed the dysregulated miRNAs in ocular sarcoidosis to search for potential biomarkers.
This study included seven patients diagnosed with ocular sarcoidosis (five definite and two presumed). Five patients with unclassified uveitis and 24 with non-inflammatory diseases served as controls. MicroRNA expression levels in vitreous humor samples were measured by microarray, and differentially expressed miRNAs between sarcoidosis and other diseases were explored. Next, pathway enrichment analysis was performed to evaluate the functions of the dysregulated miRNAs, and machine learning was used to search for candidate biomarkers.
A total of 614 upregulated miRNAs and 8 downregulated miRNAs were detected in vitreous humor of patients with ocular sarcoidosis compared with patients with unclassified uveitis and non-inflammatory diseases. Some dysregulated miRNAs were involved in the TGF-β signaling pathway. Furthermore, we identified miR-764 as the best predictor for ocular sarcoidosis using Boruta selection.
In this study, comprehensive miRNA analysis of vitreous humor samples identified dysregulated miRNAs in ocular sarcoidosis. This study suggests new insights into molecular pathogenetic mechanisms of sarcoidosis and may provide useful information toward developing novel diagnostic biomarkers and therapeutic targets for sarcoidosis.
微小RNA（miRNA）是非编码RNA，作为多种疾病的生物标志物受到关注。然而，尚未有关于结节病患者玻璃体液中miRNA的广泛无偏分析的报道。在本研究中，我们全面分析了眼部结节病中失调的miRNA，以寻找潜在的生物标志物。
本研究纳入了7例诊断为眼部结节病的患者（5例确诊，2例疑似）。5例未分类葡萄膜炎患者和24例非炎症性疾病患者作为对照。通过微阵列测量玻璃体液样本中的miRNA表达水平，探索结节病与其他疾病之间差异表达的miRNA。接下来，进行通路富集分析以评估失调miRNA的功能，并使用机器学习寻找候选生物标志物。
与未分类葡萄膜炎和非炎症性疾病患者相比，在眼部结节病患者的玻璃体液中总共检测到614个上调的miRNA和8个下调的miRNA。一些失调的miRNA参与了TGF-β信号通路。此外，我们使用Boruta选择法将miR-764鉴定为眼部结节病的最佳预测因子。
在本研究中，对玻璃体液样本进行的全面miRNA分析确定了眼部结节病中失调的miRNA。本研究为结节病的分子发病机制提供了新的见解，并可能为开发结节病的新型诊断生物标志物和治疗靶点提供有用信息。
