ArticleInvestigative ophthalmology & visual science2012
Mitochondria DNA replication and DNA methylation in the metabolic memory associated with continued progression of diabetic retinopathy.
Article in Investigative ophthalmology & visual science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 124 citations in OpenAlex.
- Epigenomic profiling reveals an association between persistence of DNA methylation and metabolic memory in the DCCT/EDIC type 1 diabetes cohort.Proceedings of the National Academy of Sciences of the United States of America · 2016Trial
- Epigenetic regulation in a high-sugar environment (Review).International journal of molecular medicine · 2026Review
- Article
- The Central Role of Oxidative Stress in Diabetic Retinopathy: Advances in Pathogenesis, Diagnosis, and Therapy.Diagnostics (Basel, Switzerland) · 2026Review
- The mechanistic interplay of reactive oxygen species in metabolic pathways and insulin signaling in type 2 diabetes.Molecular biology reports · 2025Review
- TET2 has endothelial-specific roles in interferon responses that are dysregulated by hyperglycemia in vitro and in vivo.The Journal of biological chemistry · 2025Article
- Modulation of Oxidative Stress in Diabetic Retinopathy: Therapeutic Role of Natural Polyphenols.Antioxidants (Basel, Switzerland) · 2025Review
- Epigenetic Modifications in the Retinal Pigment Epithelium of the Eye During RPE-Related Regeneration or Retinal Diseases in Vertebrates.Biomedicines · 2025Review
- Mechanism and implications of advanced glycation end products (AGE) and its receptor RAGE axis as crucial mediators linking inflammation and obesity.Molecular biology reports · 2025Review
- Circulating Cell-Free DNA as an Epigenetic Biomarker for Early Diabetic Retinopathy: A Narrative Review.Diagnostics (Basel, Switzerland) · 2025Review
- New perspectives on DNA methylation modifications in ocular diseases.International journal of ophthalmology · 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
- Metabolic memory: mechanisms and diseases.Signal transduction and targeted therapy · 2024Review
- Diabetic Retinopathy and Regulation of Mitochondrial Glutathione-Glutathione Peroxidase Axis in Hyperhomocysteinemia.Antioxidants (Basel, Switzerland) · 2024Article
- Traversing the epigenetic landscape: DNA methylation from retina to brain in development and disease.Frontiers in cellular neuroscience · 2024Review
- 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
- Advanced glycation end products regulate the receptor of AGEs epigenetically.Frontiers in cell and developmental biology · 2023Article
- Diabetic Hearts Exhibit Global DNA Hypermethylation That Alter the Mitochondrial Functional Genes to Enhance the Sensitivity of the Heart to Ischemia Reperfusion Injury.Biomedicines · 2022Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
purposeDiabetic retinopathy fails to halt after cessation of hyperglycemic insult, and a vicious cycle of mitochondria damage continues. The aim of our study was to investigate the effect of termination of hyperglycemia on retinal mtDNA replication, and elucidate the mechanism responsible for the continued mtDNA damage.
methodsPolymerase gamma 1 (POLG1), the catalytic subunit of the mitochondrial DNA replication enzyme, and the damage to the displacement loop region of mtDNA (D-loop) were analyzed in the retina from streptozotocin-diabetic rats maintained in poor glycemic control (PC, glycated hemoglobin ∼11%) or in good glycemic control (GC, glycated hemoglobin ∼6%) for 6 months, or in PC for three months followed by GC for three months (Rev). To understand the mechanism DNA methylation status of POLG1 promoter was investigated by methylation-specific PCR. The key parameters were confirmed in the isolated retinal endothelial cells exposed to high glucose, followed by normal glucose.
resultsPOLG1 continued to be down-regulated, the D-loop region damaged, and the CpG islands at the regulatory region of POLG hyper-methylated even after three months of GC that had followed three months of PC (Rev group). Similar results were observed in the retinal endothelial cells exposed to normal glucose after being exposed to high glucose.
conclusionsContinued hypermethylation of the CpG sites at the regulatory region of POLG affects its binding to the mtDNA, compromising the transcriptional activity. Modulation of DNA methylation using pharmaceutic or molecular means could help maintain mitochondria homeostasis, and prevent further progression of diabetic retinopathy.
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