CFH exerts anti-oxidant effects on retinal pigment epithelial cells independently from protecting against membrane attack complex

  • Age Related Macular Degeneration (AMD) is the first cause of social blindness in people aged over 65 leading to atrophy of retinal pigment epithelial cells (RPE), photoreceptors and choroids, eventually associated with choroidal neovascularization. Accumulation of undigested cellular debris within RPE cells or under the RPE (Drusen), oxidative stress and inflammatory mediators contribute to the RPE cell death. The major risk to develop AMD is the Y402H polymorphism of complement factor H (CFH). CFH interacting with oxidized phospholipids on the RPE membrane modulates the functions of these cells, but the exact role of CFH in RPE cell death and survival remain poorly understood. The aim of this study was to analyze the potential protective mechanism of CFH on RPE cells submitted to oxidative stress. Upon exposure to oxidized lipids 4-HNE (4-hydroxy-2-nonenal) derived from photoreceptors, both the human RPE cell line ARPE-19 and RPE cells derived from human induced pluripotent stem cells were protected from death only in the presence of the full length human recombinant CFH in the culture medium. This protective effect was independent from the membrane attack complex (MAC) formation. CFH maintained RPE cells tight junctions’ structure and regulated the caspase dependent apoptosis process. These results demonstrated the CFH anti-oxidative stress functions independently of its capacity to inhibit MAC formation.
Author:Céline Borras, Jérémie Canonica, Sylvie Jorieux, Toufk Abache, Mohamed El Sanharawi, Christophe Klein, Kimberley Delaunay, Laurent Jonet, Michèle Salvodelli, Marie-Christine Naud, Yvan Arsenijevic, Andrée Shalabi, Landry Souchaud, Francine Behar-Cohen, Virginie Dinet
Pubmed Id:
Parent Title (English):Scientific reports
Publisher:Macmillan Publishers Limited, part of Springer Nature
Place of publication:[London]
Document Type:Article
Year of Completion:2019
Date of first Publication:2019/09/25
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/10/10
Tag:Complement cascade; Visual system
Issue:1, Art. 13873
Page Number:12
First Page:1
Last Page:12
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Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0