2009 Fiscal Year Final Research Report
A novel therapeutic approach against age-related macular degeneration targeting complement activation pathway
| 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
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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 |
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| 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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[Journal Article] Absence of association between COL1A1 polymorphisms and high myopia in the Japanese population2009
Author(s)
Nakanishi H, Yamada R, Gotoh N, Hayashi H, Otani A, Tsujikawa A, Yamashiro K, Shimada N, Ohno-Matsui K, Mochizuki M, Saito M, Saito K, Iida T, Matsuda F, Yoshimura N
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Journal Title
Invest Ophthalmol Vis Sci 50
Pages: 544-550
Peer Reviewed
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[Journal Article] Altered Function of Factor I Caused by Amyloid b : Implication for Pathogenesis of age-related Macular Degeneration from Drusen2008
Author(s)
Wang J, Ohno-Matsui K, Yoshida T, Kojima A, Shimada N, Nakahama K, Safranova O, Iwata N, Saido TC, Mochizuki M, Morita I
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Journal Title
J Immunol 181
Pages: 712-720
Peer Reviewed
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[Journal Article] Cathepsin L in bone marrow-derived cells is required for retinal and choroidal neovascularization
Author(s)
Shimada N, Ohno-Matsui K, Iseki S, Koike M, Uchiyama Y, Wang J, Yoshida T, Sato T, Peters C, Mochizuki M, Morita I
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Journal Title
Peer Reviewed
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[Journal Article] A genome-wide association analysis identified a novel susceptible locus for pathological myopia at 11q24.1
Author(s)
Nakanishi H, Yamada R, Gotoh N, Hayashi H, Yamashiro K, Shimada N, Ohno-Matsui K, Mochizuki M, Saito M, Iida T, Matsuda K, Tajima K, Yoshimura N, Matsuo F
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Journal Title
Peer Reviewed
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[Journal Article] Single nucleotide polymorphisms in promoter region of matrix metalloproteinase 1, 2, and 3 in Japanese with high myopia
Author(s)
Nakanishi H, Hayashi H, Yamada R, Yamashiro K, Nakata I, Shimada N, Ohno-Matsui K, Mochizuki M, Ozaki M, Yoshitake S, Kuriyama S, saito M, Iida T, Matsuo K, Masuda F, Yoshimura N
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Journal Title
Invest Ophthalmol Vis Sci (in press)
Peer Reviewed
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