ArticleMolecular biology of the cell2015
Cholesterol-mediated activation of acid sphingomyelinase disrupts autophagy in the retinal pigment epithelium.
Article in Molecular biology of the cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
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.
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Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.
- The role of autophagy in ocular health: mechanisms, pathologies, and therapeutic strategies.Biology direct · 2026Pooled it
- Lipid-driven membrane remodeling engages a lysosome-dependent adaptive repair program during retinal aging.Molecular neurodegeneration · 2026Article
- Acid sphingomyelinase inhibition restores RPE homeostasis and photoreceptor function in preclinical Stargardt macular degeneration models.bioRxiv : the preprint server for biology · 2026Article
- Age-Driven Lipid Remodeling Activates Lysosome-Mediated Plasma Membrane Repair.Research square · 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
- Dysregulated DNA Methylation inInternational journal of molecular sciences · 2025Article
- Gene therapy for age-related macular degeneration: a promising frontier in vision preservation.Cell communication and signaling : CCS · 2025Review
- Features that distinguish age-related macular degeneration from aging.Experimental eye research · 2025Review
- Emerging roles of the acid sphingomyelinase/ceramide pathway in metabolic and cardiovascular diseases: Mechanistic insights and therapeutic implications.World journal of cardiology · 2025Review
- How crosstalk between mitochondria, lysosomes, and other organelles can prevent or promote dry age-related macular degeneration.Experimental eye research · 2025Review
- Aberrant Lipid Metabolism and Complement Activation in Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2024Review
- Impaired cathepsin D in retinal pigment epithelium cells mediates Stargardt disease pathogenesis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Article
- Bottlenecks in the Investigation of Retinal Sterol Homeostasis.Biomolecules · 2024Review
- Review
- Optineurin tunes outside-in signaling to regulate lysosome biogenesis and phagocytic clearance in the retina.Current biology : CB · 2023Article
- Retina and RPE lipid profile changes linked with ABCA4 associated Stargardt's maculopathy.Pharmacology & therapeutics · 2023Review
- Apolipoprotein ε in Brain and Retinal Neurodegenerative Diseases.Aging and disease · 2023Review
- The relevance of acid sphingomyelinase as a potential target for therapeutic intervention in hepatic disorders: current scenario and anticipated trends.Archives of toxicology · 2023Review
- Improved Lipofuscin Models and Quantification of Outer Segment Phagocytosis Capacity in Highly Polarized Human Retinal Pigment Epithelial Cultures.Journal of visualized experiments : JoVE · 2023Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
Autophagy is an essential mechanism for clearing damaged organelles and proteins within the cell. As with neurodegenerative diseases, dysfunctional autophagy could contribute to blinding diseases such as macular degeneration. However, precisely how inefficient autophagy promotes retinal damage is unclear. In this study, we investigate innate mechanisms that modulate autophagy in the retinal pigment epithelium (RPE), a key site of insult in macular degeneration. High-speed live imaging of polarized adult primary RPE cells and data from a mouse model of early-onset macular degeneration identify a mechanism by which lipofuscin bisretinoids, visual cycle metabolites that progressively accumulate in the RPE, disrupt autophagy. We demonstrate that bisretinoids trap cholesterol and bis(monoacylglycero)phosphate, an acid sphingomyelinase (ASMase) cofactor, within the RPE. ASMase activation increases cellular ceramide, which promotes tubulin acetylation on stabilized microtubules. Live-imaging data show that autophagosome traffic and autophagic flux are inhibited in RPE with acetylated microtubules. Drugs that remove excess cholesterol or inhibit ASMase reverse this cascade of events and restore autophagosome motility and autophagic flux in the RPE. Because accumulation of lipofuscin bisretinoids and abnormal cholesterol homeostasis are implicated in macular degeneration, our studies suggest that ASMase could be a potential therapeutic target to ensure the efficient autophagy that maintains RPE health.
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What Socratic holds
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 Socratic graph.