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Open AccessArticle

Oxidative Stress Increases Endogenous Complement-Dependent Inflammatory and Angiogenic Responses in Retinal Pigment Epithelial Cells Independently of Exogenous Complement Sources

1
Experimental Ophthalmology, Eye clinic, University Hospital Regensburg, 93053 Regensburg, Germany
2
R&D Department, Hycult Biotech, 5405 PD Uden, The Netherlands
3
Institute of Analytical Chemistry, Chemo- and Biosensors, University of Regensburg, 93053 Regensburg, Germany
4
Department of Ophthalmology, University Hospital of Bern and Department of Biomedical Research, University of Bern, 3010 Bern, Switzerland
*
Author to whom correspondence should be addressed.
Antioxidants 2019, 8(11), 548; https://doi.org/10.3390/antiox8110548
Received: 24 September 2019 / Revised: 30 October 2019 / Accepted: 11 November 2019 / Published: 13 November 2019
Oxidative stress-induced damage of the retinal pigment epithelium (RPE) and chronic inflammation have been suggested as major contributors to a range of retinal diseases. Here, we examined the effects of oxidative stress on endogenous complement components and proinflammatory and angiogenic responses in RPE cells. ARPE-19 cells exposed for 1–48 h to H2O2 had reduced cell–cell contact and increased markers for epithelial–mesenchymal transition but showed insignificant cell death. Stressed ARPE-19 cells increased the expression of complement receptors CR3 (subunit CD11b) and C5aR1. CD11b was colocalized with cell-derived complement protein C3, which was present in its activated form in ARPE-19 cells. C3, as well as its regulators complement factor H (CFH) and properdin, accumulated in the ARPE-19 cells after oxidative stress independently of external complement sources. This cell-associated complement accumulation was accompanied by increased nlrp3 and foxp3 expression and the subsequently enhanced secretion of proinflammatory and proangiogenic factors. The complement-associated ARPE-19 reaction to oxidative stress, which was independent of exogenous complement sources, was further augmented by the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib. Our results indicate that ARPE-19 cell-derived complement proteins and receptors are involved in ARPE-19 cell homeostasis following oxidative stress and should be considered as targets for treatment development for retinal degeneration. View Full-Text
Keywords: oxidative stress; retinal pigment epithelial cells; complement system; inflammasome; foxp3; olaparib oxidative stress; retinal pigment epithelial cells; complement system; inflammasome; foxp3; olaparib
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Trakkides, T.-O.; Schäfer, N.; Reichenthaler, M.; Kühn, K.; Brandwijk, R.J.M.G.E.; Toonen, E.J.M.; Urban, F.; Wegener, J.; Enzmann, V.; Pauly, D. Oxidative Stress Increases Endogenous Complement-Dependent Inflammatory and Angiogenic Responses in Retinal Pigment Epithelial Cells Independently of Exogenous Complement Sources. Antioxidants 2019, 8, 548.

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