Journal article
Factor-H-related protein 1 (FHR1), a promotor of para-inflammation in age-related macular degeneration
Journal of neuroinflammation, Vol.22(1), 173
07/03/2025
DOI: 10.1186/s12974-025-03499-z
PMCID: PMC12226897
PMID: 40611130
Abstract
Age-related macular degeneration (AMD), a multifactorial type of retinal degeneration represents the most common cause for blindness in elderly. Polymorphisms in complement factor-H increase, while absence of factor-H-related protein-1 (FHR1) decreases the AMD risk, currently explained by their opposing relationship. Here we identify a FHR1-driven pathway fostering chronic cellular inflammation. FHR1 accumulates below the retinal pigment epithelium (RPE) in AMD donor tissue and similarly the murine homolog, muFHR1 is abundant in three AMD-relevant mouse models. These mouse models express the muFHR1 receptor EGF-like module-containing mucin-like hormone receptor 1 (Emr1) on the RPE and on invading mononuclear phagocytes (MP), where both cells form clusters via muFHR1/Emr1. FHR1 ignited EMR2-dependent Ca
-signals and gene expression in both human RPE cell line and in vivo where muFHR1 affects Emr1
cells (RPE and MP) gene expression shown by RNAseq analysis. As muFHR1 deletion in mice revealed significantly reduced MP invasion and neoangiogenesis in laser-induced choroidal neovascularization, we hypothesize that FHR1 accumulates, stabilizes and activates MP in the stage of RPE degeneration.
Details
- Title: Subtitle
- Factor-H-related protein 1 (FHR1), a promotor of para-inflammation in age-related macular degeneration
- Creators
- Andjela Sekulic - Humboldt-Universität zu BerlinSarah M Herr - Medizinische Hochschule HannoverKelly Mulfaul - University of IowaInga-Marie Pompös - Humboldt-Universität zu BerlinSilvia Winkler - Humboldt-Universität zu BerlinCarola Dietrich - Max Delbrück CenterBenedikt Obermayer - Berlin Institute of Health at Charité - Universitätsmedizin BerlinRobert F Mullins - University of IowaThomas Conrad - Berlin Institute of Health at Charité - Universitätsmedizin BerlinPeter F Zipfel - Friedrich Schiller University JenaFlorian Sennlaub - InsermChristine Skerka - Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI)Olaf Strauß - Humboldt-Universität zu Berlin
- Resource Type
- Journal article
- Publication Details
- Journal of neuroinflammation, Vol.22(1), 173
- DOI
- 10.1186/s12974-025-03499-z
- PMID
- 40611130
- PMCID
- PMC12226897
- NLM abbreviation
- J Neuroinflammation
- ISSN
- 1742-2094
- eISSN
- 1742-2094
- Publisher
- BMC
- Grant note
- Projekt DEALGerman Research Society (DFG)German Society for Ophthalmology (DOG)ProRetina FoundationCharite Universitatsmedizin Berlin/Berlin Institute of Health at Charite
Open Access funding enabled and organized by Projekt DEAL. Open Access funding enabled and organized by Projekt DEAL. We gratefully thank the German Research Society (DFG), German Society for Ophthalmology (DOG), ProRetina Foundation as well as the Charite Universitatsmedizin Berlin/Berlin Institute of Health at Charite for the funding and support of this project. The funders did not have any role in the conceptualization, design, data collection, analysis decision to publish or preparation of the manuscript.
- Language
- English
- Date published
- 07/03/2025
- Academic Unit
- The University of Iowa Institute for Vision Research; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Ophthalmology and Visual Sciences
- Record Identifier
- 9984843239102771
Metrics
39 Record Views