ArticleThe Journal of clinical investigation2016
Reprogramming metabolism by targeting sirtuin 6 attenuates retinal degeneration.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
76 citing papers in PubMed, 107 citations in OpenAlex.
- Rod photoreceptors have a dual dependency on both aerobic glycolysis and OXPHOS and diverge metabolically from other retinal neurons.Science advances · 2026Article
- Redox imbalance dictates dependence on GOT1 versus GOT2 for rod photoreceptor health during aging and stress.Redox biology · 2026Article
- Photoreceptor deletion of pyruvate dehydrogenase E1 subunit α1 induces retinal degeneration and reprograms retinal metabolism.Molecular metabolism · 2026Article
- Redox imbalance dictates dependence on GOT1 versus GOT2 for rod photoreceptor health during aging and stress.bioRxiv : the preprint server for biology · 2026Article
- Review
- Differential effects of HDAC inhibitors in the RhoCell death discovery · 2025Article
- Nutrient supplementation mitigates retinal dysfunction in Acox1 knockout mice with impaired peroxisomal fatty acid oxidation.Journal of advanced research · 2025Article
- A Novel, Long-Acting, Small Molecule PKM2 Activator and Its Potential Broad Application Against Photoreceptor Degeneration.Translational vision science & technology · 2025Article
- Metabolic regulation of visual acuity.Science advances · 2025Article
- Pten Loss Triggers Progressive Photoreceptor Degeneration in an mTORC1-Independent Manner.Investigative ophthalmology & visual science · 2025Article
- Ablating VHL in rod photoreceptors modulates RPE glycolysis and improves preclinical model of retinitis pigmentosa.The Journal of clinical investigation · 2025Article
- Targeting miR-181a/b in retinitis pigmentosa: implications for disease progression and therapy.Cell & bioscience · 2024Article
- Gene Therapies for Retinitis Pigmentosa that Target Glucose Metabolism.Cold Spring Harbor perspectives in medicine · 2024Review
- CRISPR editing of anti-anemia drug target rescues independent preclinical models of retinitis pigmentosa.Cell reports. Medicine · 2024Article
- Dysregulation of histone deacetylases in ocular diseases.Archives of pharmacal research · 2024Review
- Metabolic transcriptomics dictate responses of cone photoreceptors to retinitis pigmentosa.Cell reports · 2023Article
- Lactate-dependent transcriptional regulation controls mammalian eye morphogenesis.Nature communications · 2023Article
- SIRT6 overexpression in the nucleus protects mouse retinal pigment epithelium from oxidative stress.Life science alliance · 2023Article
- Spatiotemporal control of genome engineering in cone photoreceptors.Cell & bioscience · 2023Article
- Pathomechanisms of Inherited Retinal Degeneration and Perspectives for Neuroprotection.Cold Spring Harbor perspectives in medicine · 2023Review
16 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
15 authors at 2 institutions in 1 country.
Funding
Abstract
Retinitis pigmentosa (RP) encompasses a diverse group of Mendelian disorders leading to progressive degeneration of rods and then cones. For reasons that remain unclear, diseased RP photoreceptors begin to deteriorate, eventually leading to cell death and, consequently, loss of vision. Here, we have hypothesized that RP associated with mutations in phosphodiesterase-6 (PDE6) provokes a metabolic aberration in rod cells that promotes the pathological consequences of elevated cGMP and Ca2+, which are induced by the Pde6 mutation. Inhibition of sirtuin 6 (SIRT6), a histone deacetylase repressor of glycolytic flux, reprogrammed rods into perpetual glycolysis, thereby driving the accumulation of biosynthetic intermediates, improving outer segment (OS) length, enhancing photoreceptor survival, and preserving vision. In mouse retinae lacking Sirt6, effectors of glycolytic flux were dramatically increased, leading to upregulation of key intermediates in glycolysis, TCA cycle, and glutaminolysis. Both transgenic and AAV2/8 gene therapy-mediated ablation of Sirt6 in rods provided electrophysiological and anatomic rescue of both rod and cone photoreceptors in a preclinical model of RP. Due to the extensive network of downstream effectors of Sirt6, this study motivates further research into the role that these pathways play in retinal degeneration. Because reprogramming metabolism by enhancing glycolysis is not gene specific, this strategy may be applicable to a wide range of neurodegenerative disorders.
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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.