| Project/Area Number |
17K16969
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Ophthalmology
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| Research Institution | Tottori University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 緑内障 / サイトカイン / IL-8 / MCP-1 / 臨床 / プロテオーム / マイクロアレイ |
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| Outline of Final Research Achievements |
In eyes with primary open angle glaucoma (POAG) or pseudoexfoliation glaucoma (PEG), the level of interleukin (IL)-1α, IL-2, IL-4, IL-8, IL-23, and monocyte chemotactic protein (MCP)-1 were significantly elevated. IL-8 had the highest odds ratio for determining the presence or absence of glaucoma. Levels of IL-8 and MCP-1 were significantly correlated with preoperative intraocular pressure or visual field defects in PEG eyes.
Structural equation modeling analysis indicated elevated IL-8 was significantly associated with poor prognosis after trabeculectomy. This suggested that IL-8 directly affects outflow tract obstruction or remodeling.When contractility and cell movement were used as in vitro model of trabecular outflow obstruction, IL-8, MCP-1, and cytomegalovirus infection activated cell-cell junctions and remodeling of cytoskeletal pathways. This pathway was suggested to play important roles in regulation of cell migration or contractility.
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| Academic Significance and Societal Importance of the Research Achievements |
緑内障の病態マーカーは、これまで報告があるが、病態において特異的に上がるサイトカイン種の解析に限られていた。しかしながら、疾患を分類し得るのみでは、それが実際に病態を反映しているのか明らかではない。本研究では、緑内障において重要な病態を代表する項目として、眼圧、視野、緑内障手術予後に関わるマーカーを抽出することを試みた。このようなマーカーは、実際に標的治療としても利用できる可能性があるため、ヒト線維柱帯細胞を用いて、その分子病態的意義まで検証を進めた。この経路の詳細な解析あるいは検証により、新たな治療薬やストラテジーの創出につながる可能性がある。
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