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

Trakkides, Timon-Orest; Schäfer, Nicole; Reichenthaler, Maria; Kühn, Konstanze; Brandwijk, Ricardo J M G E; Toonen, Erik J M; Urban, Florian; Wegener, Joachim; Enzmann, Volker; Pauly, Diana (2019). Oxidative Stress Increases Endogenous Complement-Dependent Inflammatory and Angiogenic Responses in Retinal Pigment Epithelial Cells Independently of Exogenous Complement Sources. Antioxidants, 8(11) MDPI 10.3390/antiox8110548

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ophthalmology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Augenklinik > Forschungsgruppe Augenheilkunde

UniBE Contributor:

Enzmann, Volker

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2076-3921

Publisher:

MDPI

Language:

English

Submitter:

Volker Enzmann

Date Deposited:

13 Jan 2020 16:14

Last Modified:

28 Nov 2020 02:30

Publisher DOI:

10.3390/antiox8110548

PubMed ID:

31766295

Uncontrolled Keywords:

complement system foxp3 inflammasome olaparib oxidative stress retinal pigment epithelial cells

BORIS DOI:

10.7892/boris.137022

URI:

https://boris.unibe.ch/id/eprint/137022

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