| Project/Area Number |
19390441
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
OHNO Kyoko Tokyo Medical and Dental University, 医歯学総合研究科, 准教授 (30262174)
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| Co-Investigator(Kenkyū-buntansha) |
MOCHIZUKI Manabu 東京医科歯科大学, 医歯学総合研究科, 教授 (10010464)
MORITA Ikuo 東京医科歯科大学, 医歯学総合研究科, 教授 (60100129)
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| Project Period (FY) |
2007 – 2009
|
| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2009: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2008: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2007: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
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| Keywords | 加齢黄斑変性 / 網膜色素上皮 / Amyloid β / 補体活性化 / 慢性炎症 / 網膜色素上皮細胞 / マクロファージ / ミクログリア / B因子 / サイトカイン / amyloid β / C3b / H因子 / I因子 |
|---|
| Research Abstract |
Chronic inflammation in subretinal space due to unregulated complement activation is considered to play an important role in the pathogenesis of age-related macular degeneration (AMD). In this project, we investigated how Aβ that is accumulated within drusen affects the modulators of complement activation pathway. The results showed that Aβ binds to both factor H and factor I, which are inhibitors of complement alternative pathway, and selectively inhibits the function of factor I. Aβ-stimulated RPE cells produce monocyte chemoattractant protein-1 (MCP-1), and recruit macrophages and microglia into subretinal space. Aβ-stimulated macrophages and microglia produce TNF-α and IL-1β, which then act on RPE cells and induce an up-regulation of factor B (main activator of complement alternative pathway).
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