ArticleJCI insight2018
Impaired monocyte cholesterol clearance initiates age-related retinal degeneration and vision loss.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 74 citations in OpenAlex.
- Murine models of neovascular AMD revisited: Mechanistic pathways, immune-metabolic crosstalk, and the impact of aging and sex.Experimental eye research · 2026Review
- RPE With ROCK-Mediated Epithelial-Mesenchymal Transition as a Key Contributor of Subretinal Fibrosis in AMD.Investigative ophthalmology & visual science · 2026Article
- Cholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells.Science advances · 2026Article
- The intersection of mitochondria, lipids, and ferroptosis: a new avenue for dry age-related macular degeneration.Apoptosis : an international journal on programmed cell death · 2025Review
- A Novel, Long-Acting, Small Molecule PKM2 Activator and Its Potential Broad Application Against Photoreceptor Degeneration.Translational vision science & technology · 2025Article
- Apolipoprotein M attenuates age-related macular degeneration phenotypes via sphingosine-1-phosphate signaling and lysosomal lipid catabolism.Nature communications · 2025Article
- Dietary effects on the retina of hamsters.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- The Landscape of Vascular Endothelial Growth Factor Inhibition in Retinal Diseases.Investigative ophthalmology & visual science · 2025Review
- Sialylation as a checkpoint for inflammatory and complement-related retinal diseases.Frontiers in cellular neuroscience · 2025Review
- The role of microglia in glaucoma - trigger and potential target.Frontiers in immunology · 2025Review
- Elevation of ANXA1 associated with potential protective mechanism against ferroptosis and immune cell infiltration in age-related macular degeneration.European journal of medical research · 2024Article
- Candidate SNP Markers Significantly Altering the Affinity of the TATA-Binding Protein for the Promoters of Human Genes Associated with Primary Open-Angle Glaucoma.International journal of molecular sciences · 2024Article
- Monoclonal antibodies that block Roundabout 1 and 2 signaling target pathological ocular neovascularization through myeloid cells.Science translational medicine · 2024Article
- prominin-1-null Xenopus laevis develop subretinal drusenoid-like deposits, cone-rod dystrophy and RPE atrophy.Journal of cell science · 2024Article
- Retinal pigment epithelium-specific ablation of GPx4 in adult mice recapitulates key features of geographic atrophy in age-related macular degeneration.Cell death & disease · 2024Article
- Cholesterol Accumulation Promotes Photoreceptor Senescence and Retinal Degeneration.Investigative ophthalmology & visual science · 2024Article
- Prominin-1 null Xenopus laevis develop subretinal drusenoid-like deposits, cone-rod dystrophy, and RPE atrophy.bioRxiv : the preprint server for biology · 2024Article
- LXR/CD38 activation drives cholesterol-induced macrophage senescence and neurodegeneration via NADCell reports · 2024Article
- Oxidative Stress, Persistent Inflammation and Blood Coagulation Alterations in Serum Proteome of Patients with Neovascular Age-Related Macular Degeneration.Life (Basel, Switzerland) · 2024Article
- Drusen in AMD from the Perspective of Cholesterol Metabolism and Hypoxic Response.Journal of clinical medicine · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Advanced age-related macular degeneration (AMD), the leading cause of blindness among people over 50 years of age, is characterized by atrophic neurodegeneration or pathologic angiogenesis. Early AMD is characterized by extracellular cholesterol-rich deposits underneath the retinal pigment epithelium (RPE) called drusen or in the subretinal space called subretinal drusenoid deposits (SDD) that drive disease progression. However, mechanisms of drusen and SDD biogenesis remain poorly understood. Although human AMD is characterized by abnormalities in cholesterol homeostasis and shares phenotypic features with atherosclerosis, it is unclear whether systemic immunity or local tissue metabolism regulates this homeostasis. Here, we demonstrate that targeted deletion of macrophage cholesterol ABC transporters A1 (ABCA1) and -G1 (ABCG1) leads to age-associated extracellular cholesterol-rich deposits underneath the neurosensory retina similar to SDD seen in early human AMD. These mice also develop impaired dark adaptation, a cardinal feature of RPE cell dysfunction seen in human AMD patients even before central vision is affected. Subretinal deposits in these mice progressively worsen with age, with concomitant accumulation of cholesterol metabolites including several oxysterols and cholesterol esters causing lipotoxicity that manifests as photoreceptor dysfunction and neurodegeneration. These findings suggest that impaired macrophage cholesterol transport initiates several key elements of early human AMD, demonstrating the importance of systemic immunity and aging in promoting disease manifestation. Polymorphisms in genes involved with cholesterol transport and homeostasis are associated with a significantly higher risk of developing AMD, thus making these studies translationally relevant by identifying potential targets for therapy.
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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.