ArticleInvestigative ophthalmology & visual science2014
Retinal mitochondrial DNA mismatch repair in the development of diabetic retinopathy, and its continued progression after termination of hyperglycemia.
Article in Investigative ophthalmology & visual science, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 73 citations in OpenAlex.
- The Central Role of Oxidative Stress in Diabetic Retinopathy: Advances in Pathogenesis, Diagnosis, and Therapy.Diagnostics (Basel, Switzerland) · 2026Review
- Epigenetic Modifications in the Retinal Pigment Epithelium of the Eye During RPE-Related Regeneration or Retinal Diseases in Vertebrates.Biomedicines · 2025Review
- Mitochondrial defects and metabolic vulnerabilities in Lynch syndrome-associated MSH2-deficient endometrial cancer.JCI insight · 2025Article
- Targeting oxidative stress in diabetic retinopathy: mechanisms, pathology, and novel treatment approaches.Frontiers in immunology · 2025Review
- Review
- Relationship between Biochemical Pathways and Non-Coding RNAs Involved in the Progression of Diabetic Retinopathy.Journal of clinical medicine · 2024Review
- DNA Damage and Repair in Eye Diseases.International journal of molecular sciences · 2023Review
- The impact of oxidative stress-induced mitochondrial dysfunction on diabetic microvascular complications.Frontiers in endocrinology · 2023Review
- Research highlights on contributions of mitochondrial DNA microsatellite instability in solid cancers - an overview.Contemporary oncology (Poznan, Poland) · 2022Review
- Mitochondrial Dynamics in the Metabolic Memory of Diabetic Retinopathy.Journal of diabetes research · 2022Article
- Nuclear Genome-Encoded Long Noncoding RNAs and Mitochondrial Damage in Diabetic Retinopathy.Cells · 2021Article
- Pilot Screening of Cell-Free mtDNA in NIPT: Quality Control, Variant Calling, and Haplogroup Determination.Genes · 2021Article
- The emerging relationship between metabolism and DNA repair.Cell cycle (Georgetown, Tex.) · 2021Review
- Development of novel quality control material based on CRISPR/Cas9 editing and xenografts for MLH1 protein deficiency testing.Journal of clinical laboratory analysis · 2021Article
- Does epigenetics have a role in age related macular degeneration and diabetic retinopathy?Genes & diseases · 2021Review
- Role of mismatch repair in aging.International journal of biological sciences · 2021Review
- Diabetic Retinopathy: Mitochondria Caught in a Muddle of Homocysteine.Journal of clinical medicine · 2020Review
- Epigenetics and Mitochondrial Stability in the Metabolic Memory Phenomenon Associated with Continued Progression of Diabetic Retinopathy.Scientific reports · 2020Article
- Neuroinflammation and oxidative stress act in concert to promote neurodegeneration in the diabetic retina and optic nerve: galectin-3 participation.Neural regeneration research · 2020Review
- Retinopathy in a Diet-Induced Type 2 Diabetic Rat Model and Role of Epigenetic Modifications.Diabetes · 2020Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
purposeMitochondrial DNA (mtDNA) is damaged in the retina in diabetes, and mitochondria copy numbers are decreased. The displacement-loop (D-loop) of the mtDNA, the region with transcription/replication elements, experiences more damage than other regions of mtDNA. Our aim was to examine the role of DNA mismatch repair (MMR) in mitochondria homeostasis in diabetic retinopathy, and in its continued progression after cessation of hyperglycemia.
methodsEffect of hyperglycemia on sequence variants in the D-loop region was investigated in retinal endothelial cells and in the retina from streptozotocin-induced diabetic rats using mismatch-specific surveyor nuclease. The role of MMR machinery in mtDNA damage and mitochondrial respiration was investigated in retinal endothelial cells overexpressing Mlh1, an MMR enzyme mainly associated with mtDNA polymerase gamma, or Msh2 (associated with nuclear polymerase beta).
resultsHyperglycemia increased sequence variants in the D-loop region. While overexpression of Mlh1 in endothelial cells ameliorated glucose-induced increase in D-loop sequence variants, decrease in respiration rate and increase in apoptosis, overexpression of Msh2 did not protect the mitochondria damage. Termination of hyperglycemia failed to reverse decrease in MMR enzymes and increase in D-loop sequence variants.
conclusionsDue to a compromised MMR system, the sequence variants in the D-loop region were not repaired, and that resulted in impaired mtDNA transcription. Mitochondria become dysfunctional, and they continued to be dysfunctional even after hyperglycemia was terminated, contributing to the development, and progression of diabetic retinopathy. Thus, strategies targeting mitochondrial MMR machinery could help maintain mitochondria homeostasis, and inhibit the development of diabetic retinopathy and its continued progression.
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