The DOI matches its Crossref record; 266 of the 266 references it cites were found in a registry or an index.
Revisiting the role of factor H in age-related macular degeneration: Insights from complement-mediated renal disease and rare genetic variants
Open accessAbstract
Ophthalmologists are long familiar with the eye showing signs of systemic disease, but the association between age-related macular degeneration and abnormal complement activation, common to several renal disorders, has only recently been elucidated. Although complement activation products were identified in drusen almost three decades ago, it was not until the early 21st century that a single-nucleotide polymorphism in the complement factor H gene was identified as a major heritable determinant of age-related macular degeneration, galvanizing global efforts to unravel the pathogenesis of this common disease. Advances in proteomic analyses and familial aggregation studies have revealed distinctive clinical phenotypes segregated by the functional effects of common and rare genetic variants on the mature protein and its splice variant, factor H-like protein 1. The predominance of loss-of-function, N-terminal mutations implicate age-related macular degeneration as a disease of general complement dysregulation, offering several therapeutic avenues for its modulation. Here, we explore the molecular impact of these mutations/polymorphisms on the ability of variant factor H/factor H-like protein 1 to localize to polyanions, pentraxins, proinflammatory triggers, and cell surfaces across ocular and renal tissues and exert its multimodal regulatory functions and their clinical implications. Finally, we critically evaluate key therapeutic and diagnostic efforts in this rapidly evolving field.
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“While most complement proteins are produced in the liver, others (such as C1q, C7, Factor D, and properdin) are produced at extrahepatic sites by various cells, including monocytes, macrophages, and glial and endothelial cells [7,204,205].”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [7]
In the citing paper
“and are known to be susceptible to complement dysregulation [7,209].”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [7]
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Cites
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Complement factor H polymorphism in age-related macular degeneration
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Complement factor H polymorphism and age-related macular degeneration
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Complement factor H variant increases the risk of age-related macular degeneration
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Cited by
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Hammadi, S., Tzoumas, N., Ferrara, M., Meschede, I. P., Lo, K., Harris, C., Lako, M., & Steel, D. H. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12082870 · Cited by 44
Self-citationComplement inhibitors for age-related macular degeneration
Tzoumas, N., Riding, G., Williams, M. A., & Steel, D. H. (2023) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd009300.pub3 · Cited by 38
Self-citationTzoumas, N., Kavanagh, D., Cordell, H. J., Lotery, A. J., Patel, P. J., & Steel, D. H. (2022) · Human Molecular Genetics · doi:10.1093/hmg/ddac060 · Cited by 31
Self-citation
Metadata
- Authors
- Tzoumas, N., Hallam, D., Harris, C. L., Lako, M., Kavanagh, D., & Steel, D. H. W.
- Affiliations
- Newcastle University (GB)
- Royal Victoria Infirmary (GB)
- Sunderland Eye Infirmary (GB)
- Corresponding author
- Tzoumas, Nikolaos
- Venue
- Survey of Ophthalmology
- Publisher
- Elsevier BV
- Published
- 2021-03
- Volume
- 66
- Issue
- 2
- Pages
- 378-401
- ISSN
- 0039-6257 (ISSN-L)
- OpenAlex
- W3095970076
- Cited by
- 33
- References
- 266
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 7 · 2023: 7 · 2022: 5 · 2021: 7
- FWCI
- 0.46
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Survey of Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Macular Society
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- complement factor H, age-related macular degeneration, complement activation, complement dysregulation, factor H-like protein 1, single nucleotide polymorphisms, rare variants, loss-of-function mutations, drusen, pentraxins, polyanions, complement regulation, therapeutic target, diagnosis
- MeSH terms
- Complement System Proteins, Humans, Macular Degeneration, Phenotype, Complement Factor H, Proteomics
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