| Project/Area Number |
18K09452
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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 | Health Sciences University of Hokkaido (2020-2021)
Sapporo Medical University (2018-2019) |
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Principal Investigator |
HIRAOKA Miki 北海道医療大学, 予防医療科学センター, 准教授 (80246983)
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| Co-Investigator(Kenkyū-buntansha) |
大黒 浩 札幌医科大学, 医学部, 教授 (30203748)
阿部 晃 札幌医科大学, 医学部, 講師 (70136927)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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| Keywords | 眼内炎症 / 細胞障害 / 酸化リン脂質 / マクロファージ / ぶどう膜炎 / 房水 / 細胞毒性 / 自己免疫性 |
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| Outline of Final Research Achievements |
The present study was conducted to examine the profile of oxidized phospholipids in uveitis using rat model and clinical specimens, and to elucidate the role of macrophages in the metabolism of oxidized phospholipids. Six species of oxidized phospholipids were detected in the aqueous humors of rats and humans. The content of each oxidized phospholipids was higher in the uveitis group of rat uveitis model and clinical uveitis samples. The oxidized phospholipids showed cytotoxicity to retinal epithelial cell line. The cytotoxicity was reduced by pretreatment of oxidized phospholipids with macrophages.
The oxidized phospholipids formed by intraocular inflammation could induce cytotoxicity. The present findings suggest that the phagocytic macrophages eliminate oxidized phospholipids and prevent from tissue damage following intraocular inflammation.
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| Academic Significance and Societal Importance of the Research Achievements |
ぶどう膜炎に代表される眼内炎症で、炎症が鎮静した後も眼組織に障害が残ると重篤な視機能低下をきたす。これまで眼内炎症を防ぐ、あるいは軽症化させる試みは基礎研究、臨床応用の場面でも多くなされてきた。しかし、炎症によって不可逆な細胞障害を起こす機序とその防御については十分に解明せれていない。本研究では眼内炎症で生じる酸化リン脂質がどのように細胞障害をきたすか、またそれを防ぐためにマクロファージがどのように関与しているかを示した。この結果から、酸化リン脂質の代謝を促進させることで、眼内炎症に続発する細胞障害から防御する新たな治療法の開発につながる。
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