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Open AccessArticle

Properdin Modulates Complement Component Production in Stressed Human Primary Retinal Pigment Epithelium Cells

1
Experimental Ophthalmology, Eye clinic, University Hospital Regensburg, 93053 Regensburg, Germany
2
Department of Ophthalmology, University Hospital of Bern, University of Bern, 3010 Bern, Switzerland
3
Department of Biomedical Research, University of Bern, 3010 Bern, Switzerland
*
Author to whom correspondence should be addressed.
These authors share senior authorship.
Antioxidants 2020, 9(9), 793; https://doi.org/10.3390/antiox9090793
Received: 21 July 2020 / Revised: 15 August 2020 / Accepted: 22 August 2020 / Published: 26 August 2020
(This article belongs to the Special Issue Antioxidants and Age-Related Ocular Diseases)
The retinal pigment epithelium (RPE) maintains visual function and preserves structural integrity of the retina. Chronic dysfunction of the RPE is associated with retinal degeneration, including age-related macular degeneration (AMD). The AMD pathogenesis includes both increased oxidative stress and complement dysregulation. Physiological sources of oxidative stress in the retina are well known, while complement sources and regulation are still under debate. Using human primary RPE (hpRPE) cells, we have established a model to investigate complement component expression on transcript and protein level in AMD-risk and non-risk hpRPE cells. We evaluated the effect of properdin, a complement stabilizer, on the hpRPE cell-dependent complement profile exposed to oxidative stress. hpRPE cells expressed complement components, receptors and regulators. Complement proteins were also stored and secreted by hpRPE cells. We associated AMD-risk single nucleotide polymorphisms with an increased secretion of complement factors D (CFD) and I (CFI). Furthermore, we detected hpRPE cell-associated complement activation products (C3a, C5a) independent of any extracellularly added complement system. Exogenous properdin increased the mRNA expression of CFI and CFD, but decreased levels of complement components (C1Q, C3), receptors (C3AR, C5AR1, CD11B) and inflammation-associated transcripts (NLRP3, IL1B) in hpRPE cells exposed to oxidative stress. This properdin effect was time-dependently counter regulated. In conclusion, our data unveiled a local, genotype-associated complement component production in hpRPE cells, regulated by exogenous properdin. The local complement production and activation via blood-independent mechanisms can be a new therapeutic target for AMD. View Full-Text
Keywords: retinal pigment epithelium; complement system; properdin; AMD-risk genotype; intracellular; cell-associated; inflammasome; oxidative stress; human retinal pigment epithelium; complement system; properdin; AMD-risk genotype; intracellular; cell-associated; inflammasome; oxidative stress; human
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MDPI and ACS Style

Schäfer, N.; Wolf, H.N.; Enzbrenner, A.; Schikora, J.; Reichenthaler, M.; Enzmann, V.; Pauly, D. Properdin Modulates Complement Component Production in Stressed Human Primary Retinal Pigment Epithelium Cells. Antioxidants 2020, 9, 793. https://doi.org/10.3390/antiox9090793

AMA Style

Schäfer N, Wolf HN, Enzbrenner A, Schikora J, Reichenthaler M, Enzmann V, Pauly D. Properdin Modulates Complement Component Production in Stressed Human Primary Retinal Pigment Epithelium Cells. Antioxidants. 2020; 9(9):793. https://doi.org/10.3390/antiox9090793

Chicago/Turabian Style

Schäfer, Nicole; Wolf, Hannah N.; Enzbrenner, Anne; Schikora, Juliane; Reichenthaler, Maria; Enzmann, Volker; Pauly, Diana. 2020. "Properdin Modulates Complement Component Production in Stressed Human Primary Retinal Pigment Epithelium Cells" Antioxidants 9, no. 9: 793. https://doi.org/10.3390/antiox9090793

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