Effect of CTG triplet repeat expansion in TCF4 on the pathophysiology of Fuchs endothelial corneal dystrophy
| Project/Area Number |
18K09464
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56060:Ophthalmology-related
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| Research Institution | Doshisha University |
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Principal Investigator |
Okumura Naoki 同志社大学, 生命医科学部, 教授 (10581499)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | フックス角膜内皮ジストロフィ / 角膜内皮 / TCF4 / 小胞体ストレス / トリプレットリピート病 |
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| Outline of Final Research Achievements |
Triplet repeat expansion of CTG in TCF4 was reported to be most common causative of Fuchs endothelial corneal dystrophy (FECD). However, how CTG repeat induce FECD is still unclear. In the current study, we demonstrated dysregulated genes in FECD by the use of RNAseq. Subsequently, dysregulated signaling pathways were determined based on RNAseq followed by validation study using cultured corneal endothelial cells established from the patients with FECD. Additionally, mouse model possessing CTG repeat expansion in TCF4 was generated.
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| Academic Significance and Societal Importance of the Research Achievements |
フックス角膜内皮ジストロフィ（FECD）は、TCF4遺伝子の第3イントロンにおけるCTG反復配列の伸長が多くの患者に認められるトリプレットリピート病である可能性が報告されている。一方で、CTG反復配列の伸長がどのように疾患メカニズムに関係しているかについてはほとんど分かっていない。本研究は、RNAseqにより網羅的にFECD患者由来の角膜内皮組織における遺伝子の発現変動を明らかにした。また、CTGリピートの伸張配列を有するマウスの作成に成功した。不明点の多いFECDの病態解明に大きく寄与し、さらには創薬ターゲットの同定につながる成果である考えている。
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Report
(4 results)
Research Products
(74 results)
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[Journal Article] Association of rs613872 and Trinucleotide Repeat Expansion in the TCF4 Gene of German Patients With Fuchs Endothelial Corneal Dystrophy2019
Author(s)
Okumura N, Hayashi R, Nakano M, Tashiro K, Yoshii K, Aleff R, Butz M, Highsmith EW, Wieben ED, Fautsch MP, Baratz KH, Komori Y, Ueda E, Nakahara M, Weller J, Tourtas T, Schlötzer-Schrehardt U, Kruse F, Koizumi N
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Journal Title
Cornea
Volume: 38(7)
Issue: 7
Pages: 799-805
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Effect of Trinucleotide Repeat Expansion on the Expression of TCF4 mRNA in Fuchs' Endothelial Corneal Dystrophy2019
Author(s)
Okumura N, Hayashi R, Nakano M, Yoshii K, Tashiro K, Sato T, Blake DJ, Aleff R, Butz M, Highsmith EW, Wieben ED, Fautsch MP, Baratz KH, Komori Y, Nakahara M, Tourtas T, Schlötzer-Schrehardt U, Kruse F, Koizumi N
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Journal Title
Invest Ophthalmol Vis Sci
Volume: 60(2)
Issue: 2
Pages: 779-786
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Effect of CTG repeat expansion in TCF4 on the pathophysiology of Fuchs endothelial corneal dystrophy.2020
Author(s)
Matsuo H, Okumura N, Komori Y, Tokunaga A, Nakayama G, Nakahara M, Blake DJ, Tourtas T, Schlötzer-Schrehardt U, Kruse FE, and Koizumi N
Organizer
The Association for Research in Vision and Ophthalmology (ARVO)
Related Report
Int'l Joint Research
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[Presentation] Association of trinucleotide repeat expansion length in TCF4 with the severity of Fuchs Endothelial Corneal Dystrophy2019
Author(s)
Komori Y, Okumura N, J. Weller, Nakano M, Tashiro K, Yoshii K, Aleff R, Butz M, Edward W. Highsmith EW, Wieben ED, Fautsch MP, Baratz KH, Tourtas T, Schlötzer-Schrehardt U, KruseF, Koizumi N
Organizer
The 10th EuCornea Congress Paris 2019
Related Report
Int'l Joint Research
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[Presentation] Association of rs613872 and trinucleotide repeat expansion in the TCF4 gene in Fuchs endothelial corneal dystrophy in Germany2018
Author(s)
Komori Y, Okumura N, Hayashi R, Nakano M, Tashiro K, Yoshii K, R Aleff, M Butz, E W Highsmith, E Wieben, M P Fautsch, K H Baratz, T Tourtas, U Schlotzer-Schrehardt, F E Kruse, Koizumi N
Organizer
The Association for Research in Vision and Ophthalmology 2018
Related Report
Int'l Joint Research
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