ArticleAntioxidants & redox signaling2012
Damaged mitochondrial DNA replication system and the development of diabetic retinopathy.
Article in Antioxidants & redox signaling, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 91 citations in OpenAlex.
- Metabolic Dysregulation and Oxidative Stress in Diabetic Retinopathy: Glycogen Metabolism, Mitochondrial Dysfunction, and Antioxidant Defences.Antioxidants (Basel, Switzerland) · 2026Review
- Article
- The Central Role of Oxidative Stress in Diabetic Retinopathy: Advances in Pathogenesis, Diagnosis, and Therapy.Diagnostics (Basel, Switzerland) · 2026Review
- Role of Antioxidants in Diseases and its Impact on Mitochondria with A Focus on Diabetes: An Overview.Current drug research reviews · 2026Review
- Role of MMP-9 and NF-κB in Diabetic Retinopathy: Progression and Potential Role of Bioflavonoids in the Mitigation of Diabetic Retinopathy.Current medicinal chemistry · 2025Review
- Epigenome-metabolism nexus in the retina: implications for aging and disease.Trends in genetics : TIG · 2024Review
- The potential of therapeutic strategies targeting mitochondrial biogenesis for the treatment of insulin resistance and type 2 diabetes mellitus.Archives of pharmacal research · 2024Review
- Epigenetics of the Pathogenesis and Complications of Type 2 Diabetes Mellitus.TouchREVIEWS in endocrinology · 2023Review
- Mitochondrial Genome-Encoded Long Noncoding RNA and Mitochondrial Stability in Diabetic Retinopathy.Diabetes · 2023Article
- Diabetic Retinopathy: Are lncRNAs New Molecular Players and Targets?Antioxidants (Basel, Switzerland) · 2022Review
- Review
- Long Noncoding RNAs and Mitochondrial Homeostasis in the Development of Diabetic Retinopathy.Frontiers in endocrinology · 2022Review
- Does epigenetics have a role in age related macular degeneration and diabetic retinopathy?Genes & diseases · 2021Review
- Epigenetic regulation of retinal development.Epigenetics & chromatin · 2021Review
- Role of mismatch repair in aging.International journal of biological sciences · 2021Review
- Diabetic Retinopathy: The Role of Mitochondria in the Neural Retina and Microvascular Disease.Antioxidants (Basel, Switzerland) · 2020Review
- Review
- African and Asian Mitochondrial DNA Haplogroups Confer Resistance Against Diabetic Stresses on Retinal Pigment Epithelial Cybrid Cells In Vitro.Molecular neurobiology · 2020Article
- Mitochondrial Defects Drive Degenerative Retinal Diseases.Trends in molecular medicine · 2020Review
- Mitochondrial DNA: A New Predictor of Diabetic Kidney Disease.International journal of endocrinology · 2020Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimIn the pathogenesis of diabetic retinopathy, retinal mitochondria are damaged, superoxide levels are elevated, and mitochondrial DNA (mtDNA) biogenesis is impaired. mtDNA has a noncoding region, displacement loop (D-loop), which has essential transcription and replication elements, and this region is highly vulnerable to oxidative damage. The aim of this study is to investigate the effect of diabetes on the D-loop damage and the mtDNA replication machinery.
resultsUsing retina from wild-type (WT) and mitochondrial superoxide dismutase transgenic (Tg) mice, we have investigated the effect of diabetes on retinal D-loop damage and on the replication system. The results were confirmed in the isolated retinal endothelial cells in which the DNA polymerase gamma 1 (POLG1) function was genetically manipulated. Diabetes damaged retinal mtDNA, and the damage was more at the D-loop region compared with the cytochrome B region. Gene transcripts and mitochondrial accumulation of POLG1, POLG2, and mtDNA helicase, the enzymes that form replisome to bind/unwind and extend mtDNA, were also decreased in WT-diabetic mice compared with WT-normal mice. Tg-diabetic mice were protected from diabetes-induced damage to the D-loop region. Overexpression of POLG1 prevented high glucose-induced D-loop damage. This was accompanied by a decrease in mitochondrial superoxide levels. INNOVATION AND
conclusionsIntegrity of the retinal D-loop region and the mtDNA replication play important roles in the mtDNA damage experienced by the retina in diabetes, and these are under the control of superoxide. Thus, the regulation of mtDNA replication/repair machinery has the potential to prevent mitochondrial dysfunction and the development of diabetic retinopathy.
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