| Project/Area Number |
18K09434
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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 | Tohoku University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中澤 徹 東北大学, 医学系研究科, 教授 (30361075)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | HDAC1/2阻害剤 / 網膜神経細胞死 / 酸化ストレス / 緑内障 / HDAC阻害剤 / K560 / NMDA / 網膜神経節細胞 / 神経保護 / 興奮性網膜神経細胞死 / NMDA傷害モデル |
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| Outline of Final Research Achievements |
Retinal ganglion cell (RGC) death is the symptom of glaucoma. It is thought that oxidative stress partially contributes the cell death. In this study, we investigated the effect of K560, an isozyme selective inhibitor of histone deacetylase (HDAC) 1/2, on oxidative stress-induced RGC death, and found that (1) K560 attenuated oxidative stress-induced death of dissociated retinal cells in mice, (2) K560 enhanced histone acetylation of retinal lysates prepared from mice administered with K560 intravitreally, (3) K560 inhibited oxidative stress-induced RGC death in mice. These findings suggested that K560 administration is a promising treatment for glaucoma.
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| Academic Significance and Societal Importance of the Research Achievements |
超高齢化社会を迎えた我が国では、緑内障を含む加齢性眼疾患の罹患者数が増加しており、その対策が急務となっている。本研究の結果、新規のHDAC１/2選択的阻害剤であるK560を眼内投与することで、酸化ストレス起因性の網膜神経節細胞死を抑制可能であることが示された。緑内障による視覚消失は、老後QOLを著しく低下させる恐れがあり、今後、臨床開発を進めることで、K560が緑内障治療薬の新たな選択肢となることが期待される。
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