Regulation of Ocular Surface Inflammation by miR-628 via Innate Immunity and Its Application to Novel Therapeutic Methods

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09749
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: MAYUMI Ueta 京都府立医科大学, 医学(系)研究科(研究院), 特任准教授 (60398386)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: miRNA / 自然免疫 / 眼表面炎症

Outline of Final Research Achievements

We performed plasma miRNA analysis using blood samples from patients with refractory ocular surface diseases and found that plasma miR628-3p was significantly up-regulated in patients' plasma compared to healthy controls. Comprehensive gene expression analysis of human monocyte cell lines with forced expression of miR628-3p showed that the expression of innate immunity-related genes, including TLR3, MDA5 and RIG-I, which are receptors for virus-derived double-stranded RNA, was significantly suppressed in mononuclear cells with forced miR628-3p expression. The expression of TLR3, MDA5, RIG-I and other innate immunity-related genes was significantly suppressed. The miR628-3p, which is significantly elevated in the patient's serum, negatively regulates innate immune-related genes, suggesting that the pathology may involve an abnormal regulation mechanism of the innate immune response.

Free Research Field

眼科

Academic Significance and Societal Importance of the Research Achievements

本研究は、難治性眼表面炎症疾患の病態・病因の理解、特にmiRNAを介した自然免疫制御の破綻の病態への関与を示している。特に miR-628-3p による自然免疫制御の機構を明らかにしており、難治性眼表面炎症疾患へのmiR-628-3p などのmiRNAやTLR3、MDA5, RIG-Iなどの自然免疫関連分子をターゲットにした新規治療法の開発につながるものである。