Molecular mechanism of pachychoroid spectrum disease

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09997
• 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: Osaka City University
• Principal Investigator: Honda Shigeru 大阪市立大学, 大学院医学研究科, 教授 (60283892)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Pachychoroid spectrum / 中心性漿液性脈絡網膜症 / 感受性遺伝子 / 機能解析 / コルチゾール / アルドステロン

Outline of Final Research Achievements

We have newly discovered the association between central serous chorioretinopathy (CSC), which is one of the pachychoroid spectrum diseases, and TNFRSF10A and GATA5 gene polymorphisms. It was also confirmed that the CSC-related gene SLC7A5 (protein LAT1) was upregulated by cortisol (HC) and aldosterone (ALD) in cultured retinal pigment epithelial cells (RPE). In this cell line, an increase in the amount of fluorescein (Fluo) transported from the basal side to the apical side by HC and ALD was observed, which was significantly suppressed by the LAT1 selective inhibitor.
From the above, it was shown that HC and ALD increased the amount of Fluo transported from the basal side to the apical side of the cultured RPE, which was related to SLC7A5 (LAT1).

Free Research Field

眼科学

Academic Significance and Societal Importance of the Research Achievements

Pachychoroid spectrum disease (PSD）は2015年に提唱された疾患概念で、脈絡膜厚の増加、脈絡膜血管の拡張や透過性亢進を一義的変化とする眼底後極部の細胞変性や滲出性病変の総称とされている。PSDは日本人を含むアジア人に多いことが知られているが、その背景にある分子メカニズムは殆ど明らかにされていないため、疾患の予防や治療予後の予測が困難であった。本研究では同疾患群に関連する遺伝子を同定し、一部の機能解析を行った。これによってPSDの病態理解が進むと同時に新たな治療法開発に繋がる事が期待される。