| Project/Area Number |
16K11300
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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 | Keio University |
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Principal Investigator |
Shimmura Shigeto 慶應義塾大学, 医学部(信濃町), 准教授 (00235780)
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| Co-Investigator(Kenkyū-buntansha) |
房木 ノエミ 慶應義塾大学, 医学部(信濃町), 研究員 (40278635)
羽藤 晋 慶應義塾大学, 医学部(信濃町), 特任講師 (70327542)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | フックス角膜変性症 / iPS細胞 / 再生医療 / 角膜内皮細胞 / フックス角膜内皮変性症 / 角膜 / 疾患iPS |
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| Outline of Final Research Achievements |
We newly established iPS cells from Fuchs’ corneal endothelial dystrophy (FECD) for the investigation of this disease. Three different SNPs were found in the TCF4 gene from our FECD patients. We derived neural crest cells (NCC) from iPSCs and sorted integrin alpha 4 and p75 NTR- double positive cells. We compared the characteristics of C-NCC (control normal donor iPS derived NCC) and F-NCC (FECD patient iPS derived NCC). Real time PCR showed the upregulation of the ER stress marker (CHOP) in F-NCC. Cornea endothelial cells derived from F-NCC also showed the upregulation of CHOP, GRP78 and XBP1 indicating that these cells are ideal for screening of potential new drugs.
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| Academic Significance and Societal Importance of the Research Achievements |
6人の疾患iPSより、3人の日本人においてTCF4 (rs17089925), (rs17089887), CLU (rs3087554) の3箇所にSNPs変異を認め、1人のオランダ人に おいてTCF4 (rs613872), (rs2286812)の2箇所にSNPs変異を認めた。角膜内皮誘導の結果、角膜内皮の分化マーカーに関してはオランダ人株でpItx2の発現が低いなど分化抵抗性の傾向をみとめた。小胞体ストレスについて健常人iPS由来角膜内皮細胞(C-CEC)を比較した結果、オランダ人株においても、日本人株においても小胞体ストレスマーカーCHOP, GRP78, XBP1の増加を検出した。
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