ArticleProceedings of the National Academy of Sciences of the United States of America2020
Disturbed glucose and pyruvate metabolism in glaucoma with neuroprotection by pyruvate or rapamycin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 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.
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Who cites it
85 citing papers in PubMed, 1 synthesis or guideline pooled it, 122 citations in OpenAlex.
- Systematic Review and Meta-Analysis on the Association Between Daily Niacin Intake and Glaucoma.Nutrients · 2024Pooled it
- Effects of nicotinamide supplementation in normal-tension glaucoma: a crossover placebo-controlled randomised clinical trial.The British journal of ophthalmology · 2026Trial
- Nicotinamide and Pyruvate in Open-Angle Glaucoma: A Randomized Controlled Trial on Neuroprotection-Design and Methodology.Ophthalmology. GlaucomaTrial
- Impaired regulatory T-cell-mediated immune tolerance promotes neurodegeneration in glaucoma.medRxiv : the preprint server for health sciences · 2026Article
- Redox imbalance dictates dependence on GOT1 versus GOT2 for rod photoreceptor health during aging and stress.Redox biology · 2026Article
- Schlemm's Canal Development and Implications for Glaucoma Treatment.Annual review of vision science · 2026Review
- Spatial multi-omics unveils sphingolipid metabolic reprogramming within the retinal pathological niche.iMeta · 2026Article
- Treating dysfunctional one-carbon metabolism in glaucoma.Neural regeneration research · 2026Article
- Mitochondrial dysfunction in neurodegenerative disorders: mechanisms and therapeutic advances.Molecular biomedicine · 2026Review
- Glaucoma and Autoimmunity: Immunopathogenic Mechanisms and Emerging Immunomodulatory Therapies.Biomedicines · 2026Review
- Pharmacological restoration of impaired autophagy in retinal ganglion cells prevents abnormal mitochondrial accumulation and glaucomatous neurodegeneration.Molecular neurodegeneration · 2026Article
- Acarbose modulates microglial Pkm2 acetylation to reshape immunometabolism and preserve retinal neurons after ischemia-reperfusion.Journal of neuroinflammation · 2026Article
- Vitamins and nutraceuticals in glaucoma research.European journal of ophthalmology · 2026Review
- Stretch strain shifts optic nerve head astrocyte metabolism to enrich α-ketoglutarate and the pentose phosphate pathway.Scientific reports · 2026Article
- Intraocular pressure induced blood retinal barrier compromise in mouse models and human glaucoma.Nature communications · 2026Article
- Redox imbalance dictates dependence on GOT1 versus GOT2 for rod photoreceptor health during aging and stress.bioRxiv : the preprint server for biology · 2026Article
- The 5-HT1A receptor antagonist WAY-100635 maleate promotes retinal ganglion cell differentiation and protects the retino-visual circuits.Communications medicine · 2026Article
- Energetic diversity in retinal ganglion cells is modulated by neuronal activity and correlates with resilience to degeneration.Nature communications · 2026Article
- Unveiling Systemic Biomarkers and Metabolic Mechanisms in Glaucoma Progression from Multi-Omics Insights.International journal of molecular sciences · 2026Article
- Erythropoiesis-inosine metabolic axis failure underlying retinal neurodegeneration in glaucoma: novel diagnoses and therapies.Experimental & molecular medicine · 2026Article
25 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
16 authors at 4 institutions in 3 countries.
Funding
Abstract
Intraocular pressure-sensitive retinal ganglion cell degeneration is a hallmark of glaucoma, the leading cause of irreversible blindness. Here, we used RNA-sequencing and metabolomics to examine early glaucoma in DBA/2J mice. We demonstrate gene expression changes that significantly impact pathways mediating the metabolism and transport of glucose and pyruvate. Subsequent metabolic studies characterized an intraocular pressure (IOP)-dependent decline in retinal pyruvate levels coupled to dysregulated glucose metabolism prior to detectable optic nerve degeneration. Remarkably, retinal glucose levels were elevated 50-fold, consistent with decreased glycolysis but possibly including glycogen mobilization and other metabolic changes. Oral supplementation of the glycolytic product pyruvate strongly protected from neurodegeneration in both rat and mouse models of glaucoma. Investigating further, we detected mTOR activation at the mechanistic nexus of neurodegeneration and metabolism. Rapamycin-induced inhibition of mTOR robustly prevented glaucomatous neurodegeneration, supporting a damaging role for IOP-induced mTOR activation in perturbing metabolism and promoting glaucoma. Together, these findings support the use of treatments that limit metabolic disturbances and provide bioenergetic support. Such treatments provide a readily translatable strategy that warrants investigation in clinical trials.
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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.