ArticleJCI insight2019
Serine and 1-carbon metabolism are required for HIF-mediated protection against retinopathy of prematurity.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 54 citations in OpenAlex.
- NDUFA4L2 rescues hyperoxia-induced migration defects in retinal endothelial cells by reversing isocitrate dehydrogenase flux blockade.bioRxiv : the preprint server for biology · 2026Article
- ADH1C Down-Regulation Is a Key Hypoxia Response in Colon Epithelium.The American journal of pathology · 2026Article
- <p>Prolyl hydroxylase domain proteins: Localization, regulation, function and their role in erythropoiesis (Review)</p>.Molecular medicine reports · 2026Review
- Blood acylcarnitine profile alterations and fatty acid metabolism dysregulation associated with severe retinopathy of prematurity in preterm infants.Frontiers in medicine · 2026Article
- Beyond Ornithine Metabolism in Gyrate Atrophy: Tissue-Specific Proteomic Insights into Neonatal and Adult OAT Deficiency.bioRxiv : the preprint server for biology · 2025Article
- Characterization of Hepatotropic Small Molecule Inhibitors of Hypoxia Inducible Factor Prolyl Hydroxylase in the Prevention of Oxygen-Induced Retinopathy.Journal of medicinal chemistry · 2025Article
- Semaphorin 6A phase separation sustains a histone lactylation-dependent lactate buildup in pathological angiogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Systemic regulation of retinal medium-chain fatty acid oxidation repletes TCA cycle flux in oxygen-induced retinopathy.Communications biology · 2025Article
- Review
- Epigenome-metabolism nexus in the retina: implications for aging and disease.Trends in genetics : TIG · 2024Review
- The Role of HIF-1α in Retinopathy of Prematurity: A Review of Current Literature.Journal of clinical medicine · 2024Review
- Retinopathy of Prematurity-Targeting Hypoxic and Redox Signaling Pathways.Antioxidants (Basel, Switzerland) · 2024Review
- ChREBP is activated by reductive stress and mediates GCKR-associated metabolic traits.Cell metabolism · 2024Article
- Pathologic vs. protective roles of hypoxia-inducible factor 1 in RPE and photoreceptors in wet vs. dry age-related macular degeneration.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Insights into the liver-eyes connections, from epidemiological, mechanical studies to clinical translation.Journal of translational medicine · 2023Review
- Metabolic transcriptomics dictate responses of cone photoreceptors to retinitis pigmentosa.Cell reports · 2023Article
- Blood urea nitrogen, a marker for severe retinopathy of prematurity?Journal of perinatology : official journal of the California Perinatal Association · 2023Article
- Systemic Cytokines in Retinopathy of Prematurity.Journal of personalized medicine · 2023Review
- Hyperoxia Induced Hypomyelination.Biomedicines · 2022Article
- Amino acid transporter SLC38A5 regulates developmental and pathological retinal angiogenesis.eLife · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
We determined which metabolic pathways are activated by hypoxia-inducible factor 1-mediated (HIF-1-mediated) protection against oxygen-induced retinopathy (OIR) in newborn mice, the experimental correlate to retinopathy of prematurity, a leading cause of infant blindness. HIF-1 coordinates the change from oxidative to glycolytic metabolism and mediates flux through serine and 1-carbon metabolism (1CM) in hypoxic and cancer cells. We used untargeted metabolite profiling in vivo to demonstrate that hypoxia mimesis activates serine/1CM. Both [13C6] glucose labeling of metabolites in ex vivo retinal explants as well as in vivo [13C3] serine labeling of metabolites followed in liver lysates strongly suggest that retinal serine is primarily derived from hepatic glycolytic carbon and not from retinal glycolytic carbon in newborn pups. In HIF-1α2lox/2lox albumin-Cre-knockout mice, reduced or near-0 levels of serine/glycine further demonstrate the hepatic origin of retinal serine. Furthermore, inhibition of 1CM by methotrexate blocked HIF-mediated protection against OIR. This demonstrated that 1CM participates in protection induced by HIF-1 stabilization. The urea cycle also dominated pathway enrichment analyses of plasma samples. The dependence of retinal serine on hepatic HIF-1 and the upregulation of the urea cycle emphasize the importance of the liver to remote protection of the retina.
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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.