Up-regulation of complement factor B in retinal pigment epithelial cells is accompanied by complement activation in the aged retina
Abstract
Complement activation is involved in the pathogenesis of age-related macular degeneration. How complement is activated in the retina is not known. Previously we have shown that complement factor H (CFH) is constitutively expressed by retinal pigment epithelial (RPE) cells and the production of CFH is negatively regulated by inflammatory cytokines and oxidative insults. Here we investigated the production and regulation of complement factor B (CFB) in RPE cells. Immunohistochemistry showed that CFB is expressed at low levels on the apical portion of the RPE cells in normal physiological conditions. With age, CFB expression increases and extends to the basal part of RPE cells. Confocal microscopy and real-time PCR of RPE cultures indicated that the production of CFB by RPE cells is positively regulated by TNF-alpha, IFN-gamma and long-term (30 days) photoreceptor outer segments treatments. Increased CFB expression in RPE cells in vivo is accompanied by the accumulation of complement C3 and C3a deposition at the Bruch's membrane and the basal layer of RPE cells. Our results suggest that RPE cells play important roles in regulating complement activation in the retina. Increased complement activation in the aged retina may be important for retinal homeostasis in the context of accumulating photoreceptor waste products.
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C3d and APOE are more abundant in the aged retina.
“both of which are more abundant in the aged retina and correlate with increased AMD risk (23–25).”
From Retinal polyunsaturated fatty acid supplementation reverses aging-related vision decline in mice (2025) · cites this paper as [23]
C3d and APOE correlate with increased AMD risk.
“both of which are more abundant in the aged retina and correlate with increased AMD risk (23–25).”
From Retinal polyunsaturated fatty acid supplementation reverses aging-related vision decline in mice (2025) · cites this paper as [23]
In ageing and AMD, there is increased expression of the complement protein C3 within RPE cells and on their basal membranes.
“In ageing and AMD, there is increased expression of the complement protein C3 within RPE cells and on their basal membranes [114,123].”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [123]
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- Authors
- Chen, M., Muckersie, E., Robertson, M., Forrester, J. V., & Xu, H.
- Affiliations
- University of Aberdeen (GB)
- Corresponding author
- Xu, Heping
- Venue
- Experimental Eye Research
- Publisher
- Elsevier BV
- Published
- 2008-12
- Volume
- 87
- Issue
- 6
- Pages
- 543-550
- ISSN
- 0014-4835 (ISSN-L)
- OpenAlex
- W2089275254
- Cited by
- 99
- References
- 37
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 7 · 2023: 5 · 2022: 8 · 2021: 7 · 2020: 7 · 2019: 3 · 2018: 8 · 2017: 4 · 2016: 5 · 2015: 7 · 2014: 3 · 2013: 6 · 2012: 11
- FWCI
- 4.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Eye Research (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Funders
- American Health Assistance Foundation
- Research Councils UK
- Office of Science
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- factor B, retinal pigment epithelial cells, complement activation, age-related macular degeneration, complement factor H, TNF-α, interferon-gamma, photoreceptor outer segments, Bruch's membrane, retinal homeostasis
- MeSH terms
- Aging, Animals, Cells, Cultured, Complement Pathway, Alternative, Mice, Inbred C57BL, Phagocytosis, Complement Factor B, Rod Cell Outer Segment, Tumor Necrosis Factor-alpha, Interleukin-6, Up-Regulation, Microscopy, Confocal, Inflammation Mediators, Reverse Transcriptase Polymerase Chain Reaction, Mice, Retinal Pigment Epithelium
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