ArticleThe Journal of biological chemistry2014
The retinal pigment epithelium utilizes fatty acids for ketogenesis.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.
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
124 citing papers in PubMed, 181 citations in OpenAlex.
- Early proteomic and metabolic signatures of liver and eye in OAT-deficient mice.Experimental eye research · 2026Article
- Murine models of neovascular AMD revisited: Mechanistic pathways, immune-metabolic crosstalk, and the impact of aging and sex.Experimental eye research · 2026Review
- Lipid-Retinoid Metabolic Network Links Genetic Variation to Molecular Heterogeneity in Inherited Retinal Degeneration.International journal of molecular sciences · 2026Article
- Hydroxysafflor Yellow A for Diabetic Retinopathy: A Critical Review of Retinal Neurovascular Mechanisms and Systemic-to-Ocular Pharmacokinetic Barriers.Antioxidants (Basel, Switzerland) · 2026Review
- Photoreceptor Vulnerability to Ferroptosis: Membrane Phospholipid Peroxidation, Mitochondrial Homeostasis, and RPE-Photoreceptor Coupling.Current issues in molecular biology · 2026Review
- 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
- Click chemistry of phenyl 1,2,3-triazole-2-pyridylpiperazine hybrids: synthesis, targeted anticancer activity, molecular modeling and computational studies.RSC advances · 2026Article
- Insulin production in the retina drives autocrine signalling and metabolism reprogramming of the ARPE-19, a retinal pigment epithelium cellular model.Cellular and molecular life sciences : CMLS · 2026Article
- Advances in retinal pigment epithelium transplantation for age-related macular degeneration: bridging biology to therapeutic frontiers.Stem cell research & therapy · 2026Review
- Selective deletion ofiScience · 2026Article
- β‑hydroxybutyric acid as a potential therapeutic metabolite for type 2 diabetes mellitus (Review).International journal of molecular medicine · 2026Review
- BDH1-Dependent Ketone Body Metabolism Maintains Müller Cell Homeostasis and Retinal Function.bioRxiv : the preprint server for biology · 2025Article
- Local Insulin for Local Needs? Insights into Retinal Insulin Signaling and RPE Metabolism.Biomolecules · 2025Review
- Absolute quantification of TCA cycle intermediates in mouse ocular tissues reveals distinct tissue- and sex-specific mitochondrial metabolism.bioRxiv : the preprint server for biology · 2025Article
- Not Just an Alternative Energy Source: Diverse Biological Functions of Ketone Bodies and Relevance of HMGCS2 to Health and Disease.Biomolecules · 2025Review
- RPE-specific MCT2 expression promotes cone survival in models of retinitis pigmentosa.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Retinal Pigment Epithelium Specific Metabolic Phenotypes Are Regulated by High-Mobility Group Protein N1.Investigative ophthalmology & visual science · 2025Article
- Role of RPE Phagocytosis in the Retina Metabolic Ecosystem.Advances in experimental medicine and biology · 2025Review
- Role of Microsomal Triglyceride Transfer Protein (MTP) in Lipid Processing Pathways in Retinal Pigment Epithelium.Advances in experimental medicine and biology · 2025Article
- N-Acetylcysteine Ameliorates Loss of the Electroretinogram b-wave in a Bardet-Biedl Syndrome Type 10 Mouse Model.Journal of experimental neurology · 2025Article
64 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Every day, shortly after light onset, photoreceptor cells shed approximately a tenth of their outer segment. The adjacent retinal pigment epithelial (RPE) cells phagocytize and digest shed photoreceptor outer segment, which provides a rich source of fatty acids that could be utilized as an energy substrate. From a microarray analysis, we found that RPE cells express particularly high levels of the mitochondrial HMG-CoA synthase 2 (Hmgcs2) compared with all other tissues (except the liver and colon), leading to the hypothesis that RPE cells, like hepatocytes, can produce β-hydroxybutyrate (β-HB) from fatty acids. Using primary human fetal RPE (hfRPE) cells cultured on Transwell filters with separate apical and basal chambers, we demonstrate that hfRPE cells can metabolize palmitate, a saturated fatty acid that constitutes .15% of all lipids in the photoreceptor outer segment, to produce β-HB. Importantly, we found that hfRPE cells preferentially release β-HB into the apical chamber and that this process is mediated primarily by monocarboxylate transporter isoform 1 (MCT1). Using a GC-MS analysis of (13)C-labeled metabolites, we showed that retinal cells can take up and metabolize (13)C-labeled β-HB into various TCA cycle intermediates and amino acids. Collectively, our data support a novel mechanism of RPE-retina metabolic coupling in which RPE cells metabolize fatty acids to produce β-HB, which is transported to the retina for use as a metabolic substrate.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.