ArticleNature medicine2016
Retinal lipid and glucose metabolism dictates angiogenesis through the lipid sensor Ffar1.
Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 187 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
187 citing papers in PubMed, 1 synthesis or guideline pooled it, 286 citations in OpenAlex.
- Implications of Diabetes-Induced Altered Metabolites on Retinal Neurodegeneration.Frontiers in neuroscience · 2022Pooled it
- Polyunsaturated fatty acid metabolism in the retinal pigment epithelium and its association with outer retinal disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Lipid homeostasis plays a critical role in inherited and acquired retinal diseases.Communications biology · 2026Review
- VLDLR: A Multifunctional receptor in diverse pathophysiological processes.Cell communication and signaling : CCS · 2026Review
- The roles of glycerophospholipids in the aging retina and age-related macular degeneration.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Review
- Targeting endoplasmic reticulum stress in diabetic retinopathy: mechanistic insights and emerging therapies.Biological research · 2026Review
- Levodopa Suppresses Choroidal Neovascularization Through a Tyrosinase-Dependent Dual Mechanism.Investigative ophthalmology & visual science · 2026Article
- Alpha-ketoglutarate promotes random-pattern skin flap survival by enhancing angiogenesis via PI3K/Akt/HIF-1α signaling pathway.Cell regeneration (London, England) · 2025Article
- Nutrient supplementation mitigates retinal dysfunction in Acox1 knockout mice with impaired peroxisomal fatty acid oxidation.Journal of advanced research · 2025Article
- Altered High-Density Lipoprotein Expression Pattern in the Aqueous Humor From Eyes With Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2025Article
- The Multitarget Compound ZLY032 Achieves Treatment of Chronic Wounds.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Combined dietary omega-3 and omega-6 fatty acids protect against hyperglycemia-associated retinopathy in neonatal mice.Pharmacological research · 2025Article
- Role of saturated fatty acid metabolism in posttranslational modifications of the Tau protein.Molecular and cellular biochemistry · 2025Review
- Prenatally derived macrophages support choroidal health and decline in age-related macular degeneration.The Journal of experimental medicine · 2025Article
- Metabolic reprogramming of the neovascular niche promotes regenerative angiogenesis in proliferative retinopathy.Nature communications · 2025Article
- Implications of Fatty Acids for Age-Related Macular Degeneration: Evidence and Recommendations.Cells · 2025Review
- AI Quantification of Vascular Lesions in Mouse Fundus Fluorescein Angiography.Translational vision science & technology · 2025Article
- Article
- Sustained release of a novel non-fibrate PPARα agonist from microparticles for neuroprotection in murine models of age-related macular degeneration.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Preserving blood-retinal barrier integrity: a path to retinal ganglion cell protection in glaucoma and traumatic optic neuropathy.Cell regeneration (London, England) · 2025Review
127 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
31 authors at 10 institutions in 3 countries.
Funding
Abstract
Tissues with high metabolic rates often use lipids, as well as glucose, for energy, conferring a survival advantage during feast and famine. Current dogma suggests that high-energy-consuming photoreceptors depend on glucose. Here we show that the retina also uses fatty acid β-oxidation for energy. Moreover, we identify a lipid sensor, free fatty acid receptor 1 (Ffar1), that curbs glucose uptake when fatty acids are available. Very-low-density lipoprotein receptor (Vldlr), which is present in photoreceptors and is expressed in other tissues with a high metabolic rate, facilitates the uptake of triglyceride-derived fatty acid. In the retinas of Vldlr(-/-) mice with low fatty acid uptake but high circulating lipid levels, we found that Ffar1 suppresses expression of the glucose transporter Glut1. Impaired glucose entry into photoreceptors results in a dual (lipid and glucose) fuel shortage and a reduction in the levels of the Krebs cycle intermediate α-ketoglutarate (α-KG). Low α-KG levels promotes stabilization of hypoxia-induced factor 1a (Hif1a) and secretion of vascular endothelial growth factor A (Vegfa) by starved Vldlr(-/-) photoreceptors, leading to neovascularization. The aberrant vessels in the Vldlr(-/-) retinas, which invade normally avascular photoreceptors, are reminiscent of the vascular defects in retinal angiomatous proliferation, a subset of neovascular age-related macular degeneration (AMD), which is associated with high vitreous VEGFA levels in humans. Dysregulated lipid and glucose photoreceptor energy metabolism may therefore be a driving force in macular telangiectasia, neovascular AMD and other retinal diseases.
Indexed as
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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.