Analysis on pathogenesis and risk factors of Fuchs endothelial corneal dystrophy

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09718
• 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 University
• Principal Investigator: Oie Yoshinori 大阪大学, 大学院医学系研究科, 講師 (20599881)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: フックス角膜内皮ジストロフィ

Outline of Final Research Achievements

Sixteen out of 75 patients (21%) with Fuchs endothelial corneal dystrophy (FECD) were complicated with abnormal CTG repeat (TNR) expansion of more than 50 in TCF4 gene. There were no significant differences in gender, age, a history of keratoplasty, central corneal thickness, corneal densitometry, and anterior chamber morphology between the patients with and without TNR expansion, suggesting no differences in clinical phenotype.
We assessed the instability of TNR expansion using small pool PCR in 69 patients with FECD. Abnormal TNR expansions of more than 50 in the TCF4 gene were detected in leukocyte-derived genomic DNA from 15 patients. The average maximum TNR number was 1602±1258, with an average variation of 19±15. There was a significant association between the TNR number and variation (R=0.84, p<0.05). TNR expansion was greater in corneal endothelium-derived DNA compared to peripheral blood-derived DNA.

Free Research Field

眼科学

Academic Significance and Societal Importance of the Research Achievements

今回我々は、FECD患者の中でリピート伸長と非伸長患者を比較して角膜後方散乱や前眼部光干渉断層計による前房形態について網羅的に表現型比較を行ったところ、両群に差を認めなかった。リピート非伸長患者において、隅角による角膜虹彩接触が発症要因となっているのではないかとの仮説は支持されなかった。さらにリピート異常伸長を合併しているFECD患者での体細胞のリピート不安定性を証明することができた。これらの知見によってFECDの発症メカニズムやリスクの解析が進んだことは学術的に価値が高い。これらの知見を参考にして、現在角膜内皮移植に限られる治療法が開発されれば、その社会的意義は高い。