Study on development of new therapeutic methods based on plasticity of trabecular meshwork cells
| Project/Area Number |
17K19729
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Surgery related to the biological and sensory functions and related fields
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Project Period (FY) |
2017-06-30 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 緑内障 / 線維柱帯細胞 / EMT / シュレム管内皮細胞 / TGF-β2 / 眼科学 / 線維柱帯 |
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| Outline of Final Research Achievements |
We have established a new hypothesis that epithelial-mesenchymal transition (EMT)-like changes in trabecular meshwork cells contribute to glaucoma pathology. The purpose of this study was development of new therapeutic methods based on the plasticity of cells. Trabecular meshwork cells showed EMT-like changes such as extracellular matrix production enhancement, F-actin increase and α-SMA expression enhancement upon TGF-β2 stimulation. The HDAC inhibitor vorinostat significantly suppressed these EMT-like changes. Furthermore, vorinostat significantly suppressed the increase of aqueous humor outflow resistance induced by TGF-β2 stimulation in perfusion experiments. Thus, the HDAC inhibitor vorinostat was shown to suppress the increase in aqueous humor outflow resistance induced by TGF-β2.
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| Academic Significance and Societal Importance of the Research Achievements |
線維柱帯細胞のEMT様変化が房水流出抵抗亢進を引き起こすことが基礎実験レベルではあるが示すことができ、EMTをターゲットとした創薬につながる成果と考えられる。今回評価に使用したHDAC阻害剤はEMT様変化を抑制することで房水流出改善効果が認められており、安全性等の詳細な評価は必要であるが新規眼圧下降剤のターゲットとなりえると考えられる。
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Report
(4 results)
Research Products
(6 results)
