ArticleJournal of molecular medicine (Berlin, Germany)2020
Pyruvate dehydrogenase kinase/lactate axis: a therapeutic target for neovascular age-related macular degeneration identified by metabolomics.
Article in Journal of molecular medicine (Berlin, Germany), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Physiological Hypoxia and Pharmacological HIF Stabilization Induce Distinct but Overlapping Responses in Retinal Pigment Epithelial Cells.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Photoreceptor deletion of pyruvate dehydrogenase E1 subunit α1 induces retinal degeneration and reprograms retinal metabolism.Molecular metabolism · 2026Article
- Focus on Lactate and Lactylation Modification: The Potential Role in Ophthalmic Disease Treatment.International journal of molecular sciences · 2026Review
- Genetic Evidence for Causal Effects of Blood Metabolites on Age-Related Macular Degeneration and its Subtypes.Translational vision science & technology · 2026Article
- Article
- Pyruvate dehydrogenase kinases: key regulators of cellular metabolism and therapeutic targets for metabolic diseases.Journal of physiology and biochemistry · 2025Review
- Opportunities, challenges, and difficulties in NMR-based metabolomics applied to neovascular age-related macular degeneration (nAMD) patient follow-up.Frontiers in molecular biosciences · 2024Article
- Systemic Metabolomics in a Framework of Genetics and Lifestyle in Age-Related Macular Degeneration.Metabolites · 2023Article
- Unveiling the veil of lactate in tumor-associated macrophages: a successful strategy for immunometabolic therapy.Frontiers in immunology · 2023Review
- Role of glucose metabolism in ocular angiogenesis (Review).Molecular medicine reports · 2022Review
- Metabolomics and Biomarkers in Retinal and Choroidal Vascular Diseases.Metabolites · 2022Review
- Comparative Analysis Reveals Novel Changes in Plasma Metabolites and Metabolomic Networks of Infants With Retinopathy of Prematurity.Investigative ophthalmology & visual science · 2022Article
- The Role of PKM2 in Diabetic Microangiopathy.Diabetes, metabolic syndrome and obesity : targets and therapy · 2022Review
- Plasma Metabolomics of Intermediate and Neovascular Age-Related Macular Degeneration Patients.Cells · 2021Article
- Metabolomics in Retinal Diseases: An Update.Biology · 2021Review
- Targeted Metabolomic Assessment of the Sub-Lethal Toxicity of Halogenated Acetic Acids (HAAs) toMetabolites · 2021Article
- Nuclear Magnetic Resonance Spectroscopy in Clinical Metabolomics and Personalized Medicine: Current Challenges and Perspectives.Frontiers in molecular biosciences · 2021Review
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Authors and funding
20 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neovascular age-related macular degeneration (nAMD) is the leading cause of blindness in aging populations. Here, we applied metabolomics to human sera of patients with nAMD during an active (exudative) phase of the pathology and found higher lactate levels and a shift in the lipoprotein profile (increased VLDL-LDL/HDL ratio). Similar metabolomics changes were detected in the sera of mice subjected to laser-induced choroidal neovascularization (CNV). In this experimental model, we provide evidence for two sites of lactate production: first, a local one in the injured eye, and second a systemic site associated with the recruitment of bone marrow-derived inflammatory cells. Mechanistically, lactate promotes the angiogenic response and M2-like macrophage accumulation in the eyes. The therapeutic potential of our findings is demonstrated by the pharmacological control of lactate levels through pyruvate dehydrogenase kinase (PDK) inhibition by dichloroacetic acid (DCA). Mice treated with DCA exhibited normalized lactate levels and lipoprotein profiles, and inhibited CNV formation. Collectively, our findings implicate the key role of the PDK/lactate axis in AMD pathogenesis and reveal that the regulation of PDK activity has potential therapeutic value in this ocular disease. The results indicate that the lipoprotein profile is a traceable pattern that is worth considering for patient follow-up. KEY MESSAGES: Lactate and lipoprotein profile are associated with the active phase of AMD and CNV development. Lactate is a relevant and functional metabolite correlated with AMD progression. Modulating lactate through pyruvate dehydrogenase kinase led to a decrease of CNV progression. Pyruvate dehydrogenase kinase is a new therapeutic target for neovascular AMD.
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