| Project/Area Number |
26462663
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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 | Yamaguchi University |
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Principal Investigator |
KIMURA Kazuhiro 山口大学, 医学(系)研究科(研究院), 教授 (60335255)
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| Co-Investigator(Kenkyū-buntansha) |
園田 康平 九州大学, 医学研究院, 教授 (10294943)
林 謙一郎 大阪大学, 医学系研究科, 准教授 (90238105)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | retina / fibrosis / nuclear receptor / transcription factor / RPE cell |
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| Outline of Final Research Achievements |
In this study, the purpose is that formation and contraction of the subretinal fibrosis will be clarified focused on role of nuclear receptors in retinal pigment epithelial cells and we will develop novel therapeutic drugs based on transcriptional regulation through nuclear receptors.
We have screened ligands of nuclear receptors thorough three-dimensional culture system using retinal pigment epithelial cells. As a result, we identified steroid hormones containing glucocorticoid and a female hormone. These compounds were found to inhibit gel contraction. They also suppressed the expression of alpha SMA as a marker in EMT and the expression and activation of MMPs contributed to the remodeling of extracellular matrix. Their action was partially dependent on the signaling pathway of MAPKs or NF-κB. Furthermore, ATRA, vitamin A derivative, showed the same effect as steroids. Currently, we have been studying which receptors are specific for the action of vitamin A.
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