Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Exogenous CFH Modulates Levels of Pro-Inflammatory Mediators to Prevent Oxidative Damage of Retinal Pigment Epithelial Cells with the At-Risk CFH Y402H Variant

Henry Velázquez-Soto
ORCID logo ,
Sergio Groman-Lupa
,
Marisa Cruz-Aguilar
,
Alberto Salazar
,
Juan C. Zenteno
,
Maria C. Jimenez Martinez
*
Version 1 : Received: 14 June 2023 / Approved: 15 June 2023 / Online: 15 June 2023 (13:04:50 CEST)

A peer-reviewed article of this Preprint also exists.

Velazquez-Soto, H.; Groman-Lupa, S.; Cruz-Aguilar, M.; Salazar, A.L.; Zenteno, J.C.; Jimenez-Martinez, M.C. Exogenous CFH Modulates Levels of Pro-Inflammatory Mediators to Prevent Oxidative Damage of Retinal Pigment Epithelial Cells with the At-Risk CFH Y402H Variant. Antioxidants 2023, 12, 1540. Velazquez-Soto, H.; Groman-Lupa, S.; Cruz-Aguilar, M.; Salazar, A.L.; Zenteno, J.C.; Jimenez-Martinez, M.C. Exogenous CFH Modulates Levels of Pro-Inflammatory Mediators to Prevent Oxidative Damage of Retinal Pigment Epithelial Cells with the At-Risk CFH Y402H Variant. Antioxidants 2023, 12, 1540.

Abstract

Age-related macular degeneration (AMD) is a complex, progressive degenerative retinal disease. Retinal pigment epithelial (RPE) cells play an important role in the immune defense of the eye, and their dysfunction leads to the progressive irreversible degeneration of photoreceptors. Genetic factors, chronic inflammation, and oxidative stress have been implicated in AMD pathogenesis. Oxidative stress causes RPE injury, resulting in a chronic inflammatory response and cell death. The Y402H polymorphism in the complement factor H (CFH) protein is an important risk factor for AMD. However, the functional significance of CFH Y402H polymorphism remains unclear. In the present study, we investigated the role of CFH in the proinflammatory response using an in vitro model of oxidative stress in the RPE with the at-risk CFH Y402H variant. : ARPE-19 cells with the at-risk CFH Y402H variant were highly susceptible to damage caused by oxidative stress, with increased levels of inflammatory mediators and pro-apoptotic factors that lead to cell death. Pretreatment of ARPE-19 cell cultures with exogenous CFH prior to the induction of oxidative stress prevented damage and cell death. This protective affect may be related to the negative regulation of pro-inflammatory cytokines. CFH contributes to cell homeostasis and is required to modulate the pro-inflammatory cytokine response under oxidative stress in the ARPE-19 cells with the at-risk CFH Y402H variant.

Keywords

CFH; RPE; Oxidative Stress; AMD; Cytokines; Cell Death

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF Download Supplementary

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Supplementary Files Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.