ArticleInvestigative ophthalmology & visual science2013
Epigenetic modification of Sod2 in the development of diabetic retinopathy and in the metabolic memory: role of histone methylation.
Article in Investigative ophthalmology & visual science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 135 citations in OpenAlex.
- Diabetic retinopathy: shaped by the "hidden hand" of post-translational modifications.Molecular neurodegeneration · 2026Review
- Experimental Diabetic Retinopathy in Wistar Rats Induced by Streptozotocin: A Window into Retinal Disease Progression.International journal of molecular sciences · 2026Article
- Unraveling the complexity of the histone code: implications for gene regulation and disease.Genome biology · 2026Review
- Beyond hyperglycemia: histone modification-mediated epigenetic dysregulation in diabetic retinopathy and nephropathy.Diabetology & metabolic syndrome · 2026Review
- The Central Role of Oxidative Stress in Diabetic Retinopathy: Advances in Pathogenesis, Diagnosis, and Therapy.Diagnostics (Basel, Switzerland) · 2026Review
- Metabolic reprogramming in diabetic complications: mechanisms, pathologies, and molecular evidence from multi-organ studies.Frontiers in immunology · 2026Review
- Hormonal metabolic burden in diabetic retinopathy: the diabetic retina as an endocrine-responsive target organ.Frontiers in endocrinology · 2026Review
- Neurovascular unit uncoupling in diabetic retinopathy: molecular mechanisms and stage-adapted therapeutic strategies.Frontiers in endocrinology · 2026Review
- The mechanistic interplay of reactive oxygen species in metabolic pathways and insulin signaling in type 2 diabetes.Molecular biology reports · 2025Review
- Glutathione peroxidase 3 antagonizes oxidative stress and inflammation in diabetic retinopathy via NrF2/NF-κB pathway.International ophthalmology · 2025Article
- Circulating Cell-Free DNA as an Epigenetic Biomarker for Early Diabetic Retinopathy: A Narrative Review.Diagnostics (Basel, Switzerland) · 2025Review
- Renal aging and its consequences: navigating the challenges of an aging population.Frontiers in pharmacology · 2025Review
- Targeting oxidative stress in diabetic retinopathy: mechanisms, pathology, and novel treatment approaches.Frontiers in immunology · 2025Review
- An update on chronic complications of diabetes mellitus: from molecular mechanisms to therapeutic strategies with a focus on metabolic memory.Molecular medicine (Cambridge, Mass.) · 2024Review
- Diabetic Retinopathy: New Treatment Approaches Targeting Redox and Immune Mechanisms.Antioxidants (Basel, Switzerland) · 2024Review
- Metabolic memory: mechanisms and diseases.Signal transduction and targeted therapy · 2024Review
- Role of oxidative stress in neurodegenerative disorders: a review of reactive oxygen species and prevention by antioxidants.Brain communications · 2024Review
- Epigenetic modifications and metabolic memory in diabetic retinopathy: beyond the surface.Neural regeneration research · 2023Review
- Epigenetics of the Pathogenesis and Complications of Type 2 Diabetes Mellitus.TouchREVIEWS in endocrinology · 2023Review
- The essential role of N6-methyladenosine RNA methylation in complex eye diseases.Genes & diseases · 2023Review
23 more citing papers are in PubMed but not listed here.
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2 authors at 1 institution in 1 country.
Funding
Abstract
purposeMitochondrial superoxide levels are elevated in the retina in diabetes, and their scavenging enzyme, MnSOD, becomes subnormal. The objective of this study is to investigate the role of histone methylation of Sod2, the gene that encodes MnSOD, in the development of diabetic retinopathy and in the metabolic memory phenomenon associated with its continued progression after termination of hyperglycemia.
methodsEffect of high glucose on monomethyl H3K4 (H3K4me1), dimethyl H3K4 (H3K4me2), and lysine-specific demethylase-1 (LSD1) was quantified at Sod2 by chromatin immunoprecipitation in isolated retinal endothelial cells. The role of histone methylation in the metabolic memory phenomenon was investigated in the retina of rats maintained in poor glycemic control (PC, approximately 12% glycated hemoglobin [GHb]) for 3 months followed by in good glycemic control (GC, approximately 6% GHb) for 3 months.
resultsHyperglycemia reduced H3K4me1 and -me2, and increased the binding of LSD1 and Sp1 at Sod2. Regulation of LSD1 by LSD1-siRNA ameliorated glucose-induced decrease in H3K4 methylation at Sod2, and prevented decrease in Sod2 gene expression. In rats, re-institution of GC failed to reverse decrease in H3K4me1 and -me2 at Sod2, and LSD1 remained active with increased binding of LSD1 and Sp1 at Sod2. Retina from human donors with diabetic retinopathy also had decreased H3K4me2 and increased LSD1 at Sod2.
conclusionsHistone methylation of retinal Sod2 has an important role in the development of diabetic retinopathy and in the metabolic memory phenomenon associated with its continued progression. Targeting enzymes important for histone methylation may serve as a potential therapy to halt the development of diabetic retinopathy.
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