ArticleProceedings of the National Academy of Sciences of the United States of America2015
Regulation of age-related macular degeneration-like pathology by complement factor H.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
99 citing papers in PubMed, 1 synthesis or guideline pooled it, 149 citations in OpenAlex.
- Understanding AMD by analogy: systematic review of lipid-related common pathogenic mechanisms in AMD, AD, AS and GN.Lipids in health and disease · 2018Pooled it
- Age-related macular degeneration and cerebral amyloid angiopathy have similar pathologies from cholesterol-APOE-amyloid-β-complement mediated inflammation.Progress in retinal and eye research · 2026Review
- TEP-1, a glial thioester protein is required for cilia organization and intraflagellar transport in ensheathed sensory neurons inMolecular biology of the cell · 2026Article
- Review
- TEP-1, a glial thioester protein is required for cilia organization and intraflagellar transport in ensheathed sensory neurons.bioRxiv : the preprint server for biology · 2025Article
- Complement Factor H and itsbioRxiv : the preprint server for biology · 2025Article
- Truncated complement factor H Y402 gene therapy rescues C3 glomerulonephritis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Childhood obesity directly increases age-related macular degeneration risk: the role of physiobiological and immune-metabolic function.Journal of global health · 2025Article
- Friend or foe: assessing the value of animal models for facilitating clinical breakthroughs in complement research.The Journal of clinical investigation · 2025Review
- High-Density Lipoproteins Associated with Age-Related Macular Degeneration in the All of Us Research Program.Ophthalmology · 2025Article
- Oral 8-aminoguanine against age-related retinal degeneration.Communications biology · 2025Article
- Porcine Sub-Retinal Pigment Epithelium Deposits: A Model for Dry Age-Related Macular Degeneration With Comparison to Human Drusen.Investigative ophthalmology & visual science · 2025Article
- The Landscape of Vascular Endothelial Growth Factor Inhibition in Retinal Diseases.Investigative ophthalmology & visual science · 2025Review
- Characterization of drusen formation in a primary porcine tissue culture model of dry AMD.Molecular therapy. Methods & clinical development · 2024Article
- The prion protein is required for normal responses to light stimuli by photoreceptors and bipolar cells.iScience · 2024Article
- Rodent Models of Retinal Degeneration: From Purified Cells in Culture to Living Animals.Cold Spring Harbor perspectives in medicine · 2024Review
- Aberrant Lipid Metabolism and Complement Activation in Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2024Review
- Drug Approval for the Treatment of Geographic Atrophy: How We Got Here and Where We Need to Go.American journal of ophthalmology · 2024Review
- The quantification of zebrafish ocular-associated proteins provides hints for sex-biased visual impairments and perception.Heliyon · 2024Article
- Article
39 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Complement factor H (CFH) is a major susceptibility gene for age-related macular degeneration (AMD); however, its impact on AMD pathobiology is unresolved. Here, the role of CFH in the development of AMD pathology in vivo was interrogated by analyzing aged Cfh(+/-) and Cfh(-/-) mice fed a high-fat, cholesterol-enriched diet. Strikingly, decreased levels of CFH led to increased sub-retinal pigmented epithelium (sub-RPE) deposit formation, specifically basal laminar deposits, following high-fat diet. Mechanistically, our data show that deposits are due to CFH competition for lipoprotein binding sites in Bruch's membrane. Interestingly and despite sub-RPE deposit formation occurring in both Cfh(+/-) and Cfh(-/-) mice, RPE damage accompanied by loss of vision occurred only in old Cfh(+/-) mice. We demonstrate that such pathology is a function of excess complement activation in Cfh(+/-) mice versus complement deficiency in Cfh(-/-) animals. Due to the CFH-dependent increase in sub-RPE deposit height, we interrogated the potential of CFH as a previously unidentified regulator of Bruch's membrane lipoprotein binding and show, using human Bruch's membrane explants, that CFH removes endogenous human lipoproteins in aged donors. Thus, advanced age, high-fat diet, and decreased CFH induce sub-RPE deposit formation leading to complement activation, which contributes to RPE damage and visual function impairment. This new understanding of the complicated interactions of CFH in AMD-like pathology provides an improved foundation for the development of targeted therapies for AMD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.