Mechanisms of irreversible breakdown of blood-retina barrier following pericyte deficiency
| Project/Area Number |
16H05155
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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 |
Pathological medical chemistry
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| Research Institution | Nagoya City University |
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Principal Investigator |
Uemura Akiyoshi 名古屋市立大学, 大学院医学研究科, 教授 (30373278)
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| Co-Investigator(Kenkyū-buntansha) |
西山 功一 熊本大学, 国際先端医学研究機構, 准教授 (80398221)
福嶋 葉子 大阪大学, 医学系研究科, 助教 (70647031)
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| Research Collaborator |
MURATA takahisa
ISHIGURO toshina (Oonuma toshina)
MIYATA takaki
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2018: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
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| Keywords | 血液網膜関門 / ペリサイト / 内皮細胞 / マクロファージ / 炎症 / VEGF / PlGF / angiopoietin-2 / 線維化 / 網膜色素上皮細胞 / 糖尿病網膜症 |
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| Outline of Final Research Achievements |
The blood-retina barrier (BRB) comprising of endothelial cells (ECs) and pericytes contributes to maintaining the homeostasis of neural tissues. In pericyte-deficient retinas of neonatal mice injected with an anti-PDGFRβ antibody, infiltrating macrophages produced VEGFA, which activated VEGFR2 in ECs. Macrophage-derived VEGFA and PlGF further activated VEGFR1 in an autocrine or paracrine manner, thereby facilitating cell movements. Moreover, antiopoietin-2 secreted from ECs augmented hyperpermeability, angiogenesis, and inflammation. This EC-macrophage cycle initiated by pericyte deficiency led to irreversible BRB breakdown.
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| Academic Significance and Societal Importance of the Research Achievements |
糖尿病網膜症ではペリサイトの変性・脱落により血液網膜関門が破綻するが、高血糖モデル動物ではヒト網膜症を再現できないため、その病態進展機構は不明である。本研究では、高血糖を介さずにマウス網膜血管壁のペリサイトを消失させることにより、血液網膜関門が不可逆的に破綻する細胞・分子機構を解明した。本研究の成果は糖尿病網膜症に限らず、血液脳関門の破綻をきたす中枢神経系疾患の病態解明・治療法開発に資すると期待される。
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] Inhibition of stromal cell-derived factor-1α/CXCR4 signaling restores the blood-retina barrier in pericyte-deficient mouse retinas.2018
Author(s)
Omori K, Nagata N, Kurata K, Fukushima Y, Sekihachi E, Fujii N, Namba-Hamano T, Takabatake Y, Fruttiger M, Nagasawa T, Uemura A, Murata T
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Journal Title
JCI Insight
Volume: 3
Issue: 23
Pages: 120706-120706
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Sustained inflammation after pericyte depletion induces irreversible blood-retina barrier breakdown2017
Author(s)
Ogura S, Kurata K, Hattori Y, Takase H, Ishiguro-Oonuma T, Hwang Y, Ahn S, Park I, Ikeda W, Kusuhara S, Fukushima Y, Nara H, Sakai H, Fujiwara T, Matsushita J, Ema M, Hirashima M, Minami T, Shibuya M, Takakura N, Kim P, Miyata T, Ogura Y, Uemura A
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Journal Title
JCI Insight
Volume: 2
Issue: 3
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] 糖尿病網膜症の病態・生理2016
Author(s)
植村明嘉
Organizer
第59回日本糖尿病学会シンポジウム
Place of Presentation
国立京都国際会館（京都府京都市）
Year and Date
2016-05-21
Related Report
Invited
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