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

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(9), p. 793. MDPI 10.3390/antiox9090793

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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.

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:

23 Dec 2020 13:58

Last Modified:

23 Dec 2020 13:58

Publisher DOI:

10.3390/antiox9090793

PubMed ID:

32859013

BORIS DOI:

10.7892/boris.148835

URI:

https://boris.unibe.ch/id/eprint/148835

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