ArticleJCI insight2022
Triglyceride-derived fatty acids reduce autophagy in a model of retinal angiomatous proliferation.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Association between fatty acid intake and age-related macular degeneration: a meta-analysis.Frontiers in nutrition · 2024Pooled it
- Trial
- Single-Nucleus RNA Sequencing Highlights Endothelial and Müller Cell ER Stress During Retinal Neovascularization in Vldlr-/- Mouse.Investigative ophthalmology & visual science · 2026Article
- Nutrient supplementation mitigates retinal dysfunction in Acox1 knockout mice with impaired peroxisomal fatty acid oxidation.Journal of advanced research · 2025Article
- Retinal Autophagy for Sustaining Retinal Integrity as a Proof of Concept for Age-Related Macular Degeneration.International journal of molecular sciences · 2025Review
- Association between Disorders of Lipid Metabolism and Oculopathy: An Overview.International journal of medical sciences · 2025Review
- Recent Insights into Roles of Hypoxia-Inducible Factors in Retinal Diseases.International journal of molecular sciences · 2024Review
- Iron Chelator Deferiprone Restores Iron Homeostasis and Inhibits Retinal Neovascularization in Experimental Neovascular Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2024Article
- Free Fatty Acids and Free Fatty Acid Receptors: Role in Regulating Arterial Function.International journal of molecular sciences · 2024Review
- PCYT1A deficiency disturbs fatty acid metabolism and induces ferroptosis in the mouse retina.BMC biology · 2024Article
- Untargeted and temporal analysis of retinal lipidome in bacterial endophthalmitis.Prostaglandins & other lipid mediators · 2024Review
- Metabolomics studies in common multifactorial eye disorders: a review of biomarker discovery for age-related macular degeneration, glaucoma, diabetic retinopathy and myopia.Frontiers in molecular biosciences · 2024Review
- FGF21 via mitochondrial lipid oxidation promotes physiological vascularization in a mouse model of Phase I ROP.Angiogenesis · 2023Article
- Lipid-sensor FFAR1 curbs autophagy and mitochondrial respiration in murine retinal angiomatous proliferation.Autophagy reports · 2023Article
- Article
- Metabolism and Vascular Retinopathies: Current Perspectives and Future Directions.Diagnostics (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
23 authors at 5 institutions in 2 countries.
Funding
Abstract
Dyslipidemia and autophagy have been implicated in the pathogenesis of blinding neovascular age-related macular degeneration (NV-AMD). VLDL receptor (VLDLR), expressed in photoreceptors with a high metabolic rate, facilitates the uptake of triglyceride-derived fatty acids. Since fatty acid uptake is reduced in Vldlr-/- tissues, more remain in circulation, and the retina is fuel deficient, driving the formation in mice of neovascular lesions reminiscent of retinal angiomatous proliferation (RAP), a subtype of NV-AMD. Nutrient scarcity and energy failure are classically mitigated by increasing autophagy. We found that excess circulating lipids restrained retinal autophagy, which contributed to pathological angiogenesis in the Vldlr-/- RAP model. Triglyceride-derived fatty acid sensed by free fatty acid receptor 1 (FFAR1) restricted autophagy and oxidative metabolism in photoreceptors. FFAR1 suppressed transcription factor EB (TFEB), a master regulator of autophagy and lipid metabolism. Reduced TFEB, in turn, decreased sirtuin-3 expression and mitochondrial respiration. Metabolomic signatures of mouse RAP-like retinas were consistent with a role in promoting angiogenesis. This signature was also found in human NV-AMD vitreous. Restoring photoreceptor autophagy in Vldlr-/- retinas, either pharmacologically or by deleting Ffar1, enhanced metabolic efficiency and suppressed pathological angiogenesis. Dysregulated autophagy by circulating lipids might therefore contribute to the energy failure of photoreceptors driving neovascular eye diseases, and FFAR1 may be a target for intervention.
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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.