Involvement of endoplasmic reticulum stress in the pathophysiology of Fuchs endothelial corneal dystrophy
| Project/Area Number |
16K11307
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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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| Research Field |
Ophthalmology
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| Research Institution | Doshisha University |
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Principal Investigator |
Koizumi Noriko 同志社大学, 生命医科学部, 教授 (20373087)
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| Research Collaborator |
Okumura Naoki
Sato Takahiko
Friedrich Kruse
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | Fuchs角膜内皮ジストロフィ / 小胞体ストレス / 角膜内皮障害 / 薬物治療 / TGF-βシグナル / 細胞・組織 |
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| Outline of Final Research Achievements |
Fuchs endothelial corneal dystrophy (FECD) is a bilateral, progressive corneal endothelial disease. Corneal transplantation is the only current treatment option, though a pharmaceutical therapy has been anticipated. In this study, we showed that unfolded protein accumulates in the endoplasmic reticulum (ER) of corneal endothelial cells in FECD patients, and that unfolded protein progressively induces corneal endothelial cell (CEC) death via ER stress. We also showed the possibility of a pharmaceutical treatment of FECD by preventing the ER stress and apoptosis of CECs by using transforming growth factor beta (TGF-β) signaling inhibitors.
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| Academic Significance and Societal Importance of the Research Achievements |
FECDの病態の詳細は不明であり薬物療法は存在せず、現在の治療法は角膜移植のみである。本研究によってFECDの病態が解明され、保存的治療法によって角膜内皮障害の進行を遅らせることができれば、多くの患者が生涯にわたって角膜移植を行わず良好な視力を維持することができる。また、角膜移植に代わる点眼治療薬の開発は、患者の身体的・経済的負担を軽減するのみならず、医療費削減、ドナー角膜の有効利用につながり、社会福祉に貢献する極めて重要性の高い研究である。
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Report
(4 results)
Research Products
(34 results)
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[Journal Article] Sustained activation of the unfolded protein response induces cell death in Fuchs endothelial corneal dystrophy2017
Author(s)
Okumura N, Kitahara M, Okuda H, Hashimoto K, Ueda E, Nakahara N, Kinoshita S, Young RD, Quantock AJ, Tourtas T, Schlötzer-Schrehardt U, Kruse FE, Koizumi N
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Journal Title
Invest Ophthalmol
Volume: 58（9）
Issue: 9
Pages: 3697-3707
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Activation of TGF-β signaling induces cell death via the unfolded protein response in Fuchs endothelial corneal dystrophy2017
Author(s)
Okumura N, Hashimoto K, Kitahara M, Okuda H, Ueda E, Watanabe K, Nakahara M, Sato T, Kinoshita S, Tourtas T, Schlötzer-Schrehardt U, Kruse FE, Koizumi N
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Journal Title
Sci Rep
Volume: 7（1）
Issue: 1
Pages: 6801-6801
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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