The role of ATX-LPA pathway on the pathology of IOP elevation in glaucoma

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09965
• 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: The University of Tokyo
• Principal Investigator: HONJO MEGUMI 東京大学, 医学部附属病院, 准教授 (60399350)
• Co-Investigator(Kenkyū-buntansha): 相原 一 東京大学, 医学部附属病院, 教授 (80222462) ; 木村 麗子 (山岸麗子) 東京大学, 医学部附属病院, 特任研究員 (80704642)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 緑内障 / 眼圧 / 房水 / 生理活性脂質 / 線維柱帯

Outline of Final Research Achievements

We focused on lysophosphatidic acid (LPA) and the autotaxin (ATX), which are involved in fibrosis, and showed a significant increase of ATX-LPA pathway in glaucomatous eyes, especially in secondary glaucoma (with high intraocular pressure). We also found that the ATX-LPA pathway showed a significant correlation with higher intraocular pressure. From there, we further compared and examined the balance between TGFβ2 and ATX in each glaucoma subtypes, and clarified that the ATX-TGFβ2 balance is useful for diagnosing glaucoma subtypes. We also reported that the significant correlation was found between the upregulation of ATX and high IOP in the cytomegalovirus (CMV) -positive Posner-Schlossmann syndrome (PSS) that are prone to intractable glaucoma among secondary glaucoma.

Free Research Field

眼科

Academic Significance and Societal Importance of the Research Achievements

緑内障眼での眼圧上昇は主流出路流出抵抗増大によるとされ、隅角線維柱帯（TM）の線維化、細胞外マトリックス(ECM)の異常沈着、バリア機能亢進等に房水中の生理活性物質の関与が指摘されている。特にTGFβ2は開放隅角緑内障（POAG）での房水中高値が報告されているが、非常な眼圧高値を示す続発緑内障(SOAG)や落屑症候群(XFG)では低値であり、これらの病型で眼圧上昇に関わる因子は不明であった。各緑内障病型における眼圧上昇機序の詳細が判明すれば、予後予測、新しい治療開発などの可能性が期待できると考えられた。