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| Item Type: | Article |
|---|---|
| Title: | Factor-H-related protein 1 (FHR1), a promotor of para-inflammation in age-related macular degeneration |
| Creators Name: | Sekulic, Andjela, Herr, Sarah M., Mulfaul, Kelly, Pompös, Inga-Marie, Winkler, Silvia, Dietrich, Carola, Obermayer, Benedikt, Mullins, Robert F., Conrad, Thomas, Zipfel, Peter F., Sennlaub, Florian, Skerka, Christine and Strauß, Olaf |
| 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(2+)-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. |
| Keywords: | Age-Related Macular Degeneration, Retinal Pigment Epithelium, Complement System, Inflammation, Animals, Mice |
| Source: | Journal of Neuroinflammation |
| ISSN: | 1742-2094 |
| Publisher: | BioMed Central |
| Volume: | 22 |
| Number: | 1 |
| Page Range: | 173 |
| Date: | 3 July 2025 |
| Official Publication: | https://doi.org/10.1186/s12974-025-03499-z |
| PubMed: | View item in PubMed |
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