2019 Fiscal Year Final Research Report
Functional analysis of NMNAT1 in human iPS cell-derived retinal organoids development
| Project/Area Number |
18K16919
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56060:Ophthalmology-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Keywords | レーバー先天性黒内障 / 網膜変性疾患 / 網膜オルガノイド / NMNAT1 / NAD |
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| Outline of Final Research Achievements |
Leber congenital amaurosis (LCA), one of inherited retinal degenerative diseases, results in severe vision loss or blindness at early ages of life. However the molecular mechanisms by which NMNAT1 mutations cause the degeneration are unclear. In this study, I evaluated the development and maintenance of retinal organoids (RO) derived form NMNAT1 deficient iPS cells. Morphological observation revealed the area of presumptive retina was reduced in NMNAT1 deficient RO at early developental stage compared to that of control. Immunohistochemistry and gene expression analysis showed the decrease in the area of presumptive retina was caused by the excessive promotion of neural differentiation. This model facilitates to investigate the role of NMNAT1 in human retinal development.
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| Free Research Field |
眼科学
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| Academic Significance and Societal Importance of the Research Achievements |
LCAは小児の遺伝性網膜変性疾患で根治療法は確立されていない。NMNAT1はLCAの原因遺伝子として近年同定されたが、組織ユビキタスな発現を示すNMNAT1の変異がどのようにして網膜特異的な変性を引き起こすのかは不明であり、その分子機構を明らかにすることが重要である。また、オルガノイドは発生・疾患・再生・薬物評価といった多岐に渡る研究分野において有用なモデルとして利用されはじめている。申請者はNMNAT1変異により生じるLCA発症機構の解明を目指し、NMNAT1欠損ヒトiPS細胞由来の網膜オルガノイドを樹立した。このモデルにより、ヒト網膜発生過程でのNMNAT1の機能解析が可能となった。
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