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The Role of Mitochondria-Associated Reactive Oxygen Species in the Amyloid β Induced Production of Angiogenic Factors b y ARPE-19 Cells

[ Vol. 17 , Issue. 2 ]

Author(s):

L. Wu, X. Tan, L. Liang, H. Yu, C. Wang, D. Zhang, A. Kijlstra and P. Yang   Pages 140 - 148 ( 9 )

Abstract:


Objective: This study aimed to investigate the mechanisms whereby Amyloidbeta (Aβ) induces the production of angiogenic factors by a human retinal pigment epithelial cell line (ARPE-19) cells.

Methods: ARPE-19 cells obtained from the American Type Culture Collection (ATCC) were utilized in this study. The expression level of vascular endothelial growth factor (VEGF), Interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and complement activation fragments C3a and C5a were measured by Real-time quantitative PCR (RT-PCR) and Enzyme-linked immunosorbent assay (ELISA). The production of mitochondria-associated reactive oxygen species (ROS) was measured by flow cytometry.

Results: The expression of VEGF, IL-8, MCP-1, C3a and C5a was significantly increased in Aβ-treated ARPE-19 cells. Mitochondria-associated ROS production was also significantly increased when exposed to Aβ. Inhibition of mitochondrial ROS with Diphenyleneiodonium chloride (DPI) markedly decreased the Aβ induced production of VEGF, IL-8, MCP-1, C3a and C5a by ARPE-19 cells. Anti-C3a or anti-C5a neutralizing antibodies did not have a detectable influence on the secretion of VEGF, IL-8 and MCP-1 by ARPE-19 cells upon stimulation with Aβ.

Conclusion: Our results support the hypothesis that Aβ is involved in the pathogenesis of choroidal neovascularization (CNV) formation by promoting the production of the angiogenic cytokines VEGF, IL-8 and MCP-1 by RPE cells. Mitochondrial ROS was shown to play a role in the regulation of Aβ induced expression of these cytokines.

Keywords:

Amyloid-β, drusen, choroidal neovascularization, retinal pigment epithelium, age-related macular degeneration, mitochondria-associated reactive oxygen species.

Affiliation:

The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing, Eye Research Institute Maastricht, Department of Ophthalmology, University Hospital Maastricht, Maastricht, The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1, Chongqing 400016, People's



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