Title:The Role of Mitochondria-Associated Reactive Oxygen Species in the Amyloid β Induced Production of Angiogenic Factors b y ARPE-19 Cells
Volume: 17
Issue: 2
Author(s): L. Wu, X. Tan, L. Liang, H. Yu, C. Wang, D. Zhang, A. Kijlstra and P. Yang*
Affiliation:
- The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1, Chongqing 400016, People's,China
Keywords:
Amyloid-β, drusen, choroidal neovascularization, retinal pigment epithelium, age-related macular
degeneration, mitochondria-associated reactive oxygen species.
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.
