2022 Fiscal Year Final Research Report
Developing a method to regulate intraocular pathological blood vessels by targeting AM-RAMP2 and AM2-RAMP2 systems.
| Project/Area Number |
20K09803
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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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| Review Section |
Basic Section 56060:Ophthalmology-related
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| Research Institution | Shinshu University |
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Principal Investigator |
Shindo Yuka 信州大学, 医学部, 研究員 (50507506)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 滲出型加齢黄斑変性 / アドレノメデュリン / アドレノメデュリン2 / RAMP2 |
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| Outline of Final Research Achievements |
In this study, to elucidate the pathophysiological significance of the bioactive peptides adrenomedullin (AM), adrenomedullin 2 (AM2), a member of the AM family, and their partially shared receptor activity-modifying protein, RAMP2, in neovascular age-related macular degeneration, we generated laser-induced choroidal neovascularization (LI-CNV) model using knockout mice of each.
In AM, AM2, and RAMP2 knockout mice, pathological angiogenesis was expanded and inflammation and fibrosis were exacerbated, whereas exogenous administration of AM or AM2 suppressed subretinal fibrosis by suppressing epithelial-mesenchymal transition (EMT) of retinal pigment epithelial cells.
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| Free Research Field |
眼科学
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| Academic Significance and Societal Importance of the Research Achievements |
滲出型加齢黄斑変性では、脈絡膜から網膜に向かって病的な脈絡膜新生血管が発生する。滲出型加齢黄斑変性における病的新生血管は構造が脆弱であり、血管透過性が高く、浮腫や出血を生じやすい。さらに血管外滲出物貯留は慢性炎症の原因となり、過剰な創傷治癒反応の結果として網膜下の線維化を生じ、これらが黄斑部に及ぶと重篤な視力障害の原因となる。
今回の研究において、AMやAM2の外因性の投与により、LI-CNVの病態が改善されたことから、両者は新たな血管制御因子として、滲出型加齢黄斑変性に対する治療標的となることが期待される。
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