ArticleInvestigative ophthalmology & visual science2013
Transcription factor Nrf2-mediated antioxidant defense system in the development of diabetic retinopathy.
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 122 papers.
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Who cites it
122 citing papers in PubMed, 212 citations in OpenAlex.
- Oxidative Stress and Uveitis: Molecular Mechanisms and Pathogenetic Role.Current issues in molecular biology · 2026Review
- Targeting of Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) Signaling Pathway in Age-Related Eye Diseases: Molecular Mechanisms and Opportunities for therapy.Journal of biochemical and molecular toxicology · 2026Review
- Advanced azelaic acid hyalubilosome-loaded microneedles for potent anti-inflammatory, antioxidant, and antimicrobial for Acne treatment by up-regulation of Nrf2/HO-1 signaling pathway.International journal of pharmaceutics: X · 2026Article
- Eyedrop Administration of DPP-4 Inhibitors: A New Strategy for Treating Early Stages of Diabetic Retinal Disease.International journal of molecular sciences · 2026Review
- Beyond hyperglycemia: histone modification-mediated epigenetic dysregulation in diabetic retinopathy and nephropathy.Diabetology & metabolic syndrome · 2026Review
- Role of NADPH Oxidases as Novel Therapeutic Targets for the Impaired Neurovascular Unit in the Early Stage of Diabetic Retinopathy.International journal of molecular sciences · 2026Review
- The Central Role of Oxidative Stress in Diabetic Retinopathy: Advances in Pathogenesis, Diagnosis, and Therapy.Diagnostics (Basel, Switzerland) · 2026Review
- Review: The role of microglia in diabetic retinopathy and its potential as a therapeutic target.Molecular vision · 2026Review
- The pivotal role of immunometabolism in diabetic neuropathy and its potential therapeutic strategies.Frontiers in endocrinology · 2026Review
- Aloesin activates Nrf2 signaling to attenuate obesity-associated oxidative stress and hepatic steatosis in high-fat diet-fed rats.Scientific reports · 2025Article
- Inhibition of Cullin3 Neddylation Alleviates Diabetic Retinopathy by Activating Nrf2 Signaling to Combat ROS-Induced Oxidative Stress and Inflammation.Inflammation · 2025Article
- Mitochondrial transport of glutathione in diabetic retinopathy.Free radical biology & medicine · 2025Article
- Oxidative Stress and Complement Activation in Aqueous Cells and Vitreous from Patient with Vitreoretinal Diseases: Comparison Between Diabetic ERM and PDR.Antioxidants (Basel, Switzerland) · 2025Article
- Pathophysiological Mechanisms of Diabetes-Induced Macrovascular and Microvascular Complications: The Role of Oxidative Stress.Medical sciences (Basel, Switzerland) · 2025Review
- The role of microglia in the development of diabetic retinopathy and its potential clinical application.Human cell · 2025Review
- Inhibition of microRNA-139-5p by glucagon-like peptide-1 ameliorates oxidative stress-induced vascular endothelial cell damage via targeting SOD1/GCLc.Endocrine connections · 2025Article
- Unraveling the Beneficial Role of Resveratrol in Fructose-Induced Non-Alcoholic Steatohepatitis with a Focus on the AMPK/Nrf2 Signaling Axis.Medicina (Kaunas, Lithuania) · 2025Article
- The Role of Dietary Anthocyanins for Managing Diabetes Mellitus-Associated Complications.Current diabetes reviews · 2025Review
- Blast-Overpressure Induced Modulation of PARP-SIRT-NRF2 Axis in Stress Signaling of Astrocytes and Microglia.Immunity, inflammation and disease · 2025Article
- Extracellular Vesicles Derived from Adipose-Derived Mesenchymal Stem Cells Alleviate Apoptosis and Oxidative Stress of Retinal Pigment Epithelial Cells Through Activation of Nrf2 Signaling Pathway.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2024Article
62 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
purposeIncrease in reactive oxygen species (ROS) is one of the major retinal metabolic abnormalities associated with the development of diabetic retinopathy. NF-E2-related factor 2 (Nrf2), a redox sensitive factor, provides cellular defenses against the cytotoxic ROS. In stress conditions, Nrf2 dissociates from its cytosolic inhibitor, Kelch like-ECH-associated protein 1 (Keap1), and moves to the nucleus to regulate the transcription of antioxidant genes including the catalytic subunit of glutamylcysteine ligase (GCLC), a rate-limiting reduced glutathione (GSH) biosynthesis enzyme. Our aim is to understand the role of Nrf2-Keap1-GCLC in the development of diabetic retinopathy.
methodsEffect of diabetes on Nrf2-Keap1-GCLC pathway, and subcellular localization of Nrf2 and its binding with Keap1 was investigated in the retina of streptozotocin-induced diabetic rats. The binding of Nrf2 at GCLC was quantified by chromatin immunoprecipitation technique. The results were confirmed in isolated retinal endothelial cells, and also in the retina from human donors with diabetic retinopathy.
resultsDiabetes increased retinal Nrf2 and its binding with Keap1, but decreased DNA-binding activity of Nrf2 and also its binding at the promoter region of GCLC. Similar impairments in Nrf2-Keap1-GCLC were observed in the endothelial cells exposed to high glucose and in the retina from donors with diabetic retinopathy. In retinal endothelial cells, glucose-induced impairments in Nrf2-GCLC were prevented by Nrf2 inducer tBHQ and also by Keap1-siRNA.
conclusionsDue to increased binding of Nrf2 with Keap1, its translocation to the nucleus is compromised contributing to the decreased GSH levels. Thus, regulation of Nrf2-Keap1 by pharmacological or molecular means could serve as a potential adjunct therapy to combat oxidative stress and inhibit the development of diabetic retinopathy.
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