ArticleMolecular neurobiology2019
DNA Methylation-a Potential Source of Mitochondria DNA Base Mismatch in the Development of Diabetic Retinopathy.
Article in Molecular neurobiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 62 citations in OpenAlex.
- When Mitochondria Falter, the Barrier Fails: Mechanisms of Inner Blood-Retinal Barrier (iBRB) Injury and Opportunities for Mitochondria-Targeted Repair.International journal of molecular sciences · 2025Review
- Modulation of Oxidative Stress in Diabetic Retinopathy: Therapeutic Role of Natural Polyphenols.Antioxidants (Basel, Switzerland) · 2025Review
- Pathophysiological Mechanisms of Diabetes-Induced Macrovascular and Microvascular Complications: The Role of Oxidative Stress.Medical sciences (Basel, Switzerland) · 2025Review
- DNA methylation of long noncoding RNA cytochrome B in diabetic retinopathy.Non-coding RNA research · 2025Article
- Advances in molecular epidemiology of diabetic retinopathy: from genomics to gut microbiomics.Molecular biology reports · 2025Review
- Mitochondrial DNA variants in the pathogenesis and metabolic alterations of diabetes mellitus.Molecular genetics and metabolism reports · 2025Review
- Aqueous Humor Metabolomics in Different Stages of Diabetic Retinopathy Based on Ultra - Performance Liquid Chromatography - Tandem Mass Spectrometry.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- "Hyperglycemic Memory": Observational Evidence to Experimental Inference.Current diabetes reviews · 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
- DNA methyltransferase expression (DNMT1, DNMT3a and DNMT3b) as a potential biomarker for anti-VEGF diabetic macular edema response.European journal of ophthalmology · 2023Article
- Epigenetic modifications and metabolic memory in diabetic retinopathy: beyond the surface.Neural regeneration research · 2023Review
- Hypoxia-induced transcriptional differences in African and Asian versus European diabetic cybrids.Scientific reports · 2023Article
- DNA Damage and Repair in Eye Diseases.International journal of molecular sciences · 2023Review
- DNA methylation in diabetic retinopathy: pathogenetic role and potential therapeutic targets.Cell & bioscience · 2022Review
- Research Progress on Mitochondrial Dysfunction in Diabetic Retinopathy.Antioxidants (Basel, Switzerland) · 2022Review
- Targeted Mitochondrial Epigenetics: A New Direction in Alzheimer's Disease Treatment.International journal of molecular sciences · 2022Review
- Epigenetic modifications in metabolic memory: What are the memories, and can we erase them?American journal of physiology. Cell physiology · 2022Review
- Epigenetic modifications in diabetes.Metabolism: clinical and experimental · 2022Review
- Mitochondrial Dynamics in the Metabolic Memory of Diabetic Retinopathy.Journal of diabetes research · 2022Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
In the development of diabetic retinopathy, retinal mitochondria are dysfunctional, and mitochondrial DNA (mtDNA) is damaged with increased base mismatches and hypermethylated cytosines. DNA methylation is also a potential source of mutation, and in diabetes, the noncoding region, the displacement loop (D-loop), experiences more methylation and base mismatches than other regions of the mtDNA. Our aim was to investigate a possible crosstalk between mtDNA methylation and base mismatches in the development of diabetic retinopathy. The effect of inhibition of Dnmts (by 5-aza-2'-deoxycytidine or Dnmt1-siRNA) on glucose-induced mtDNA base mismatches was investigated in human retinal endothelial cells by surveyor endonuclease digestion and validated by Sanger sequencing. The role of deamination factors on increased base mismatches was determined in the cells genetically modulated for mitochondrial superoxide dismutase (Sod2) or cytidine-deaminase (APOBEC3A). The results were confirmed in an in vivo model using retinal microvasculature from diabetic mice overexpressing Sod2. Inhibition of DNA methylation, or regulation of cytosine deamination, significantly inhibited an increase in base mismatches at the D-loop and prevented mitochondrial dysfunction. Overexpression of Sod2 in mice also prevented diabetes-induced D-loop hypermethylation and increase in base mismatches. The crosstalk between DNA methylation and base mismatches continued even after termination of hyperglycemia, suggesting its role in the metabolic memory phenomenon associated with the progression of diabetic retinopathy. Inhibition of DNA methylation limits the availability of methylated cytosine for deamination, suggesting a crosstalk between DNA methylation and base mismatches. Thus, regulation of DNA methylation, or its deamination, should impede the development of diabetic retinopathy by preventing formation of base mismatches and mitochondrial dysfunction.
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