2009 Fiscal Year Final Research Report
Redox regulation of complement activation in age related macular degeneration.
| Project/Area Number |
20791262
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Ophthalmology
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| Research Institution | Kumamoto University |
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Principal Investigator |
INOMATA Yasuya Kumamoto University, 大学院・生命科学研究部, 助教 (50452884)
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| Project Period (FY) |
2008 – 2009
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| Keywords | 加齢黄斑変性症 / 補体 / チオレドキシン / LOX-1 / レドックス制御 |
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| Research Abstract |
We examined the role of thioredoxin-1 (TRX-1), an endogenous protein with a variety of redox-related roles, in the formation of choroidal neovascularization (CNV). TRX-1-associated proteins from human plasma were isolated by two-dimensional gel electrophoresis with the use of a column coupled with a mutant TRX-1 and were identified by mass spectrometry and proteomics analysis. Complement activation was determined by a fluid-phase. In human plasma, five proteins associated with TRX-1 were identified as apolipoprotein A-I, the CD5 antigen-like member of the scavenger receptor, cysteine-rich superfamily fibrinogen, albumin, and complement factor H (CFH). TRX-1 inhibited the alternative pathway C3 convertase, and its effect was additive with CFH. CNV was induced by laser photocoagulation of the ocular fundus in wild-type and transgenic mice overexpressing human TRX-1 (TRX-1 Tg). Mice were injected intraperitoneally with TRX-1, mutant TRX, or vehicle. The incidence of CNV was evaluated by lectin staining. The incidence of laser-induced CNV was reduced in TRX-1 Tg mice and in C57B/6 mice treated with TRX-1 but not in mutant TRX-1 compared with wild-type mice. Additionally, we elucidated the role of the scavenger receptor, lectin-like oxidized low-density lipoprotein receptor type 1 (LOX-1), in the formation of CNV. In wild-type mice, the relative expression level of LOX-1 mRNA compared with the control increased significantly 6 hours after laser injury and peaked 12 hours after laser injury. At 3 days after laser injury, increases in MCP-1 and VEGF significantly decreased in LOX-1-deficient mice compared with wild-type mice. Morphometric analyses revealed that the induction of CNV formation was significantly inhibited in LOX-1-deficient mice.
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[Journal Article] Suppression of choroidal neovascularization in lectin-like oxidized low density lipoprotein type-1-deficient mice2009
Author(s)
Inomata Y, Fukushima M, Hara R, Takahashi E, Honjo M, Koga T, Kawaji T, Satoh H, Takeya M, Sawamura T, Tanihara H
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Journal Title
Investigative Ophthalmology and Visual Science 50
Pages: 3970-3976
Peer Reviewed
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