ArticleThe Journal of biological chemistry2020
High-density lipoproteins are a potential therapeutic target for age-related macular degeneration.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
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
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Recent Advances in Proteomics-Based Approaches to Studying Age-Related Macular Degeneration: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- CETP Renaissance with Obicetrapib.Current atherosclerosis reports · 2026Review
- 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
- Predictive lipidaemic and clinical factors for PVR formation after RRD surgery in nondiabetic patients.International journal of ophthalmology · 2026Article
- Altered High-Density Lipoprotein Expression Pattern in the Aqueous Humor From Eyes With Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2025Article
- Truncated complement factor H Y402 gene therapy rescues C3 glomerulonephritis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- HDL proteome: from its characterization to quantitative measurements in particle subspecies and functional associations.Expert review of proteomics · 2025Review
- Apolipoprotein M attenuates age-related macular degeneration phenotypes via sphingosine-1-phosphate signaling and lysosomal lipid catabolism.Nature communications · 2025Article
- Bruch's membrane heparan sulfate retains lipoproteins in the early stages of age-related macular degeneration.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- High-Density Lipoproteins Associated with Age-Related Macular Degeneration in the All of Us Research Program.Ophthalmology · 2025Article
- Pyruvate and related energetic metabolites modulate resilience against high genetic risk for glaucoma.eLife · 2025Article
- Pyruvate and Related Energetic Metabolites Modulate Resilience Against High Genetic Risk for Glaucoma.bioRxiv : the preprint server for biology · 2025Article
- Genotype-Phenotype Correlations and Genetic Risk Assessment in Age-Related Macular Degeneration.Advances in experimental medicine and biology · 2025Review
- A high-fat plus high-sucrose diet induces age-related macular degeneration in an experimental rabbit model.Disease models & mechanisms · 2024Article
- Aberrant Lipid Metabolism and Complement Activation in Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2024Review
- Rodent Models of Retinal Degeneration: From Purified Cells in Culture to Living Animals.Cold Spring Harbor perspectives in medicine · 2024Review
- Drug Approval for the Treatment of Geographic Atrophy: How We Got Here and Where We Need to Go.American journal of ophthalmology · 2024Review
- Article
- Oxidative Stress, Persistent Inflammation and Blood Coagulation Alterations in Serum Proteome of Patients with Neovascular Age-Related Macular Degeneration.Life (Basel, Switzerland) · 2024Article
- Obicetrapib: Reversing the Tide of CETP Inhibitor Disappointments.Current atherosclerosis reports · 2024Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Strong evidence suggests that dysregulated lipid metabolism involving dysfunction of the retinal pigmented epithelium (RPE) underlies the pathogenesis of age-related macular degeneration (AMD), the leading cause of irreversible blindness in the elderly. A hallmark of AMD is the overproduction of lipid- and protein-rich extracellular deposits that accumulate in the extracellular matrix (Bruch's membrane (BrM)) adjacent to the RPE. We analyzed apolipoprotein A-1 (ApoA-1)-containing lipoproteins isolated from BrM of elderly human donor eyes and found a unique proteome, distinct from high-density lipoprotein (HDL) isolated from donor plasma of the same individuals. The most striking difference is higher concentrations of ApoB and ApoE, which bind to glycosaminoglycans. We hypothesize that this interaction promotes lipoprotein deposition onto BrM glycosaminoglycans, initiating downstream effects that contribute to RPE dysfunction/death. We tested this hypothesis using two potential therapeutic strategies to alter the lipoprotein/protein profile of these extracellular deposits. First, we used short heparan sulfate oligosaccharides to remove lipoproteins already deposited in both the extracellular matrix of RPE cells and aged donor BrM tissue. Second, an ApoA-1 mimetic, 5A peptide, was demonstrated to modulate the composition and concentration of apolipoproteins secreted from primary porcine RPE cells. Significantly, in a mouse model of AMD, this 5A peptide altered the proteomic profile of circulating HDL and ameliorated some of the potentially harmful changes to the protein composition resulting from the high-fat, high-cholesterol diet in this model. Together, these results suggest that targeting HDL interactions with BrM represents a new strategy to slow AMD progression in humans.
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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.