| Project/Area Number |
18H04062
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
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| Research Institution | Osaka University (2020-2021)
Niigata University (2018-2019) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
澤村 晴志朗 大阪大学, 医学系研究科, 助教 (10781974)
増田 正次 杏林大学, 医学部, 准教授 (20317225)
田中 謙二 慶應義塾大学, 医学部(信濃町), 教授 (30329700)
神崎 晶 慶應義塾大学, 医学部(信濃町), 講師 (50286556)
崔 森悦 新潟大学, 自然科学系, 准教授 (60568418)
任 書晃 岐阜大学, 大学院医学系研究科, 教授 (80644905)
永森 收志 東京慈恵会医科大学, 医学部, 准教授 (90467572)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥43,680,000 (Direct Cost: ¥33,600,000、Indirect Cost: ¥10,080,000)
Fiscal Year 2021: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2020: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000)
Fiscal Year 2019: ¥15,730,000 (Direct Cost: ¥12,100,000、Indirect Cost: ¥3,630,000)
Fiscal Year 2018: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
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| Keywords | 内耳 / 難聴 / 光遺伝学 / 薬剤誘導性遺伝子制御 |
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| Outline of Final Research Achievements |
Hearing loss induced by disorder of the cochlea of the inner ear affects ~10% of the global population and thus it provides a great clinical impact. The onset and progress are characterized by different time course―sudden or slow type. Fluctuating type often becomes severe and irreversible deafness. To overcome this deafness type, in the present study we described two deaf animal models by genetic modifications targeting stria vascularis, an epithelial tissue that maintains unique ionic and electrical properties of the cochlea. The mouse line showed slowly progressing hearing loss in response to drug-induced knockdown of an ion transporter in the stria. The other line expressed a light-gated ion channel in the stria and exhibited sudden deafness by optogenetic stimulation. In both mouse types, hearing was recovered after cessation of the perturbation. We also revealed a mechanism underlying hearing loss in each model. This work may contribute to translational research for deafness.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、ヒトで見られる変動性難聴の症状を模倣する「緩徐進行型」難聴および「急性発症型」難聴の動物モデルを樹立した。これらのモデルは、内耳蝸牛の電気的環境を司る上皮様組織「血管条」の機能を、それぞれ薬物投与および光照射によって制御することで、聴力の悪化と回復を反復させることができる、これまでにない難聴モデルである。本研究の成果は、症状の反復によって難聴が重症化および難治化する機序の解明や、変動性難聴の治療・予防法開発に貢献することが期待される。
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