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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/3584

Title: Effects of concentration of amyloid β (Aβ) on viability of cultured retinal pigment epithelial cells.
Other Titles: 培養網膜色素上皮に与えるアミロイドβ濃度の影響
Authors: Masuda, Naonori
Tsujinaka, Hiroki
Hirai, Hiromasa
Yamashita, Mariko
Ueda, Tetsuo
Ogata, Nahoko
Keywords: Age-related macular degeneration
Amyloid beta
Retinal pigment epithelial cells
Vascular endothelial growth factor
Pigment epithelium-derived factor
Receptor for advanced glycation end products
Issue Date: 8-Mar-2019
Publisher: BioMed Central
Citation: BMC ophthalmology Vol.19 No.1 Article No.70 (2019 Mar)
Abstract: 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.
Description: 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.
URI: http://hdl.handle.net/10564/3584
ISSN: 14712415
Academic Degrees and number: 24601A712
Degree-granting date: 2019-06-26
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2019年度

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