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In this study, we developed an experimental CRVO model in mice and evaluated the therapeutic potential of the pleiotropic peptide adrenomedullin (ADM) and its receptor activity modifying protein 2 (RAMP2). The CRVO model, which had phenotypes resembling those seen in the clinic, was produced by combining i.p. injection of Rose bengal, a photoactivator dye enhancing thrombus formation, with laser photocoagulation. Retinal vascular area, analyzed using fluorescein angiography and fluorescein isothiocyanate perfused retinal flat mounts, was decreased after induction of CRVO but gradually recovered from day 1 to 7. Measurements of retinal thickness using optical coherence tomography and histology revealed prominent edema early after CRVO, followed by gradual atrophy. Reperfusion after CRVO was diminished in Adm and Ramp2 knockout (KO) mice but was increased by exogenous ADM administration. CRVO also increased expression of a coagulation factor, oxidative stress markers, and a leukocyte adhesion molecule in both wild-type and Adm KO mice, and the effect was more pronounced in Adm KO mice. Using retinal capillary endothelial cells, ADM was found to directly suppress retinal endothelial injury. 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Development of a novel model of central retinal vascular occlusion and the therapeutic potential of the adrenomedullin-RAMP2 system(網膜中心血管閉塞モデルの新規開発とアドレノメデュリン-RAMP2系の治療応用への可能性)
http://hdl.handle.net/10091/00021490
http://hdl.handle.net/10091/00021490145545aa-f73f-4cef-bcca-14855d638659
名前 / ファイル | ライセンス | アクション |
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2019-06-14 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Development of a novel model of central retinal vascular occlusion and the therapeutic potential of the adrenomedullin-RAMP2 system(網膜中心血管閉塞モデルの新規開発とアドレノメデュリン-RAMP2系の治療応用への可能性) | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_db06 | |||||
タイプ | doctoral thesis | |||||
アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
著者 |
平林, 一貴
× 平林, 一貴 |
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出版者 | ||||||
出版者 | 信州大学 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 平林 一貴. Development of a novel model of central retinal vascular occlusion and the therapeutic potential of the adrenomedullin-RAMP2 system(網膜中心血管閉塞モデルの新規開発とアドレノメデュリン-RAMP2系の治療応用への可能性). 信州大学, 2019, 博士論文. | |||||
書誌情報 |
発行日 2019-03-31 |
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学位授与番号 | ||||||
学位授与番号 | 13601甲第1149号 | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2019-03-31 | |||||
学位名 | ||||||
学位名 | 博士(医学) | |||||
学位授与機関 | ||||||
学位授与機関識別子Scheme | kakenhi | |||||
学位授与機関識別子 | 13601 | |||||
学位授与機関名 | 信州大学(Shinshu university) | |||||
学位の区分 | ||||||
doctoral | ||||||
学位の分野 | ||||||
医学 | ||||||
学位の報告番号 | ||||||
甲第1149号 | ||||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 雑誌に発表。AMERICAN JOURNAL OF PATHOLOGY. 189(2):449-466 (2019); doi:10.1016/j.ajpath.2018.10.021. | |||||
資源タイプ(コンテンツの種類) | ||||||
内容記述タイプ | Other | |||||
内容記述 | Thesis | |||||
PubMed | ||||||
識別子タイプ | PMID | |||||
関連識別子 | https://pubmed.ncbi.nlm.nih.gov/30658846/ | |||||
関連名称 | 30658846 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1016/j.ajpath.2018.10.021 | |||||
関連名称 | 10.1016/j.ajpath.2018.10.021 | |||||
権利 | ||||||
権利情報 | © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | |||||
出版タイプ | ||||||
出版タイプ | NA | |||||
出版タイプResource | http://purl.org/coar/version/c_be7fb7dd8ff6fe43 | |||||
WoS | ||||||
Web of Science | ||||||
URL | http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000458713400019 |