Effects of concentration of amyloid β (Aβ) on viability of cultured retinal pigment epithelial cells.

• Material Type: 博士論文
• Title: Effects of concentration of amyloid β (Aβ) on viability of cultured retinal pigment epithelial cells.
• Author/Editor: Masuda, Naonori; Tsujinaka, Hiroki; Hirai, Hiromasa; Yamashita, Mariko; Ueda, Tetsuo; Ogata, Nahoko
• Author Heading: Masuda, Naonori; Tsujinaka, Hiroki; Hirai, Hiromasa; Yamashita, Mariko; Ueda, Tetsuo; Ogata, Nahoko
• Publication, Distribution, etc.: BioMed Central
• Publication Date: 2019-03-08
• Publication Date (W3CDTF): 2019-03-08
• Alternative Title: 培養網膜色素上皮に与えるアミロイドβ濃度の影響
• Periodical title: BMC ophthalmology
• No. or year of volume/issue: 19 1
• Volume: 19
• Issue: 1
• Pages: Article No.70-
• ISSN (Periodical Title): ISSN : 1471-2415
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2019-06-26
• Dissertation Number: 甲第712号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Age-related macular degeneration; Amyloid beta; Retinal pigment epithelial cells; Vascular endothelial growth factor; Pigment epithelium-derived factor; Receptor for advanced glycation end products
• Target Audience: 一般
• Note (General): type:Thesis; BACKGROUND: Amyloid beta (Aβ) is a constituent of drusen that is a common sign of age-related macular degeneration (AMD). The purpose of this study was to investigate the effect of Aβ on human retinal pigment epithelial (RPE) cells in culture. METHODS: Cells from a human RPE cell line (ARPE-19) were exposed to 0 to 25 μM of Aβ 1-40 for 48 h, and the number of living cells was determined by WST-8 cleavage. Replicative DNA synthesis was measured by the incorporation of 5'-bromo-2'-deoxyuridine. The cell death pathway was investigated by the WST-8 cleavage assay after the addition of caspase-9 inhibitor, an anti-apoptotic factor. Real-time qRT-PCR was performed using Aβ-exposed cellular RNA to determine the level of vascular endothelial growth factor (VEGF)-A and pigment epithelium derived factor (PEDF). To determine the effect of receptor-for-advanced glycation end products (RAGE), the siRNA for RAGE was inserted into ARPE-19 treated with Aβ, and the levels of expression of VEGF-A and PEDF were determined. RESULTS: The number of living ARPE-19 cells was increased by exposure to 5 μM Aβ but was decreased by exposure to 25 μM of Aβ. Replicative DNA synthesis by ARPE-19 cells exposed to 25 μM of Aβ was significantly decreased indicating that 25 μM of Aβ inhibited cell proliferation. Real-time RT-PCR showed that the level of the mRNA of PEDF was increased by exposure to 5 μM Aβ, and the levels of the mRNAs of PEDF and VEGF-A were also increased by exposure to 25 μM Aβ. The addition of an inhibitor of caspase-9 blocked the decrease the number of ARPE-19 cells exposed to 25 μM Aβ. Exposure to si-RAGE attenuated the increase of VEGF-A and PEDF mRNA expression in ARPE-19 exposed to Aβ. CONCLUSIONS: Exposure of ARPE-19 cells to low concentrations of Aβ increases the level of PEDF which then inhibits the apoptosis of ARPE-19 cells leading to RPE cell proliferation. Exposure to high concentrations of Aβ induces RPE cell death and enhances the expression of the mRNA of VEGF-A in RPE cells. The Aβ-RAGE pathway may lead to the expression VEGF-A and PEDF in RPE cells. These results suggest that Aβ is strongly related to the pathogenesis of choroidal neovascularization.; 博士（医学）・甲第712号・令和元年6月26日; © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.; © 2019 BioMed Central Ltd unless otherwise stated. Part of Springer Nature.; identifier:BMC ophthalmology Vol.19 No.1 Article No.70 (2019 Mar); identifier:14712415; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3584; identifier:BMC ophthalmology, 19(1): Article No.70
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1186/s12886-019-1076-3
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU

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http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3584/1/01%e7%94%b2712%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf fulltext

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