The molecular basis of danger signal perception by retinal pigment epithelium (RPE) cells in the pathogenesis of age-related macular degeneration
| Project/Area Number |
23592580
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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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| Research Field |
Ophthalmology
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
HAMURO Junji 京都府立医科大学, 医学(系)研究科(研究院), 教授 (80536095)
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| Co-Investigator(Renkei-kenkyūsha) |
YAMADA Jun 明治国際医療大学, 教授 (80351352)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 網膜色素上皮組織 / 局所危険感知 / 組織線維化 / 活性化マクロファージ亜集団 / マイクロRNA / 補体活性化抑制因子 / 炎症増悪回路 / miRNA / リンパ管新生 / 加齢黄斑変性 / サイトカイン / 網膜色素上皮 / マクロファージ |
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| Research Abstract |
In this study, the detailed roles of the inducer of selective apoptosis in activated macrophages in inhibiting the production of TNF-alpha and of the new HDAC inhibitor in inhibiting the TNF-alpha-induced fibrosis of RPE cells were investigated. The synergy between TNF-alpha and the HDAC inhibitor in the blockade of the formation of the vicious inflammatory cycle between RPE cells and the subpopulation of macrophages was indicated. The new molecular mechanism in danger perception mediated by miRNA secreted from RPE cells was first clarified, and the secreted miRNA was found to possibly propagate the degeneration of RPE cells in a paracrine manner. The classical and newly discovered regulators of complement activation, i.e., CFH, CD46, CD59, clusterin, and CTRP6, were found to be produced upon TNF-alpha triggered inflammatory stimuli on RPE cells. The characteristic features of the expression of these regulators in human anterior eye tissues were confirmed immunohistologically.
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Report
(4 results)
Research Products
(30 results)
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[Journal Article] Simultaneous analysis of multiple cytokines in the vitreous of patients with sarcoid uveitis2012
Author(s)
Nagata K, Maruyama K, Uno K, Shinomiya K, Yoneda K, Hamuro J, Sugita S, Yoshimura T, Sonoda KH, Mochizuki M, Kinoshita S
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Journal Title
Invest Ophthalmol Vis Sci
Volume: 53
Pages: 3827-33
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Peer Reviewed
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[Presentation] The role of cell to cell interaction through extracellular microvesicles, miRNA and exosome in deregulated functions of RPE and macrophages2014
Author(s)
Mukai A, Asada K, Toda M, Yamada J, Hatanaka H, Yamagishi T, Nagata K, Ueno M, J.Hamuro, S.Kinoshita
Organizer
ARVO2014
Place of Presentation
Orland. FL. U.S.A.
Year and Date
2014-05-06
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[Presentation] Internal analysis of gene signature and microRNA expression of cultured human corneal endothelial cell in relation to their function, cell senescense, epithelial-mesenchymal transition and fibrosis2013
Author(s)
Kazuko Asada, Munetoyo Toda, Kana Nakata, Michio Hagiya, Morio Ueno, Naoki Okumura, Noriko Koizumi, Takahiro Nakamura, Junji Hamuro and Shigeru Kinoshita
Organizer
85th Annual meeting of the ARVO (Association for Research in Vision and Ophthalmology)
Place of Presentation
Seattle. WS. U.S.A.
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