ArticleJournal of lipid research2015
A lipidomic screen of hyperglycemia-treated HRECs links 12/15-Lipoxygenase to microvascular dysfunction during diabetic retinopathy via NADPH oxidase.
Article in Journal of lipid research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 74 citations in OpenAlex.
- Deletion of GPR39 Prevents Pulmonary Arterial Hypertension by Attenuating Hypoxia-Induced Aberrant Signaling.bioRxiv : the preprint server for biology · 2026Article
- Understanding the Molecular Basis of Pathological Retinal Angiogenesis: Roles of Lipids, Non-Coding RNAs, and Cellular Crosstalk.Investigative ophthalmology & visual science · 2026Review
- The Central Role of Oxidative Stress in Diabetic Retinopathy: Advances in Pathogenesis, Diagnosis, and Therapy.Diagnostics (Basel, Switzerland) · 2026Review
- Lipoxin A4 (LXA4) as a Potential Drug for Diabetic Retinopathy.Medicina (Kaunas, Lithuania) · 2025Review
- Article
- Cysteine Leukotriene Receptor Antagonist-Montelukast Effects on Diabetic Retinal Microvascular Endothelial Cells Curtail Autophagy.Investigative ophthalmology & visual science · 2024Article
- PMToxicology and applied pharmacology · 2024Article
- Deletion of myeloid HDAC3 promotes efferocytosis to ameliorate retinal ischemic injury.Journal of neuroinflammation · 2024Article
- The relationship of redox signaling with the risk for atherosclerosis.Frontiers in pharmacology · 2024Review
- Triciribine attenuates pathological neovascularization and vascular permeability in a mouse model of proliferative retinopathy.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- Hyperglycemia and Oxidative Stress: An Integral, Updated and Critical Overview of Their Metabolic Interconnections.International journal of molecular sciences · 2023Review
- Article
- A review on the relationship between Arachidonic acid 15-Lipoxygenase (ALOX15) and diabetes mellitus.PeerJ · 2023Review
- Increased serum 12-hydroxyeicosatetraenoic acid levels are correlated with an increased risk of diabetic retinopathy in both children and adults with diabetes.Acta diabetologica · 2022Article
- Hyperhomocysteinemia dysregulates plasma levels of polyunsaturated fatty acids-derived eicosanoids.Life research · 2022Article
- A Hypothesis From Metabolomics Analysis of Diabetic Retinopathy: Arginine-Creatine Metabolic Pathway May Be a New Treatment Strategy for Diabetic Retinopathy.Frontiers in endocrinology · 2022Review
- Effects of Arachidonic Acid Metabolites on Cardiovascular Health and Disease.International journal of molecular sciences · 2021Review
- Diminished retinal complex lipid synthesis and impaired fatty acid β-oxidation associated with human diabetic retinopathy.JCI insight · 2021Article
- The Vitreous Ecosystem in Diabetic Retinopathy: Insight into the Patho-Mechanisms of Disease.International journal of molecular sciences · 2021Review
- Diabetic Retinopathy and NADPH Oxidase-2: A Sweet Slippery Road.Antioxidants (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Retinal hyperpermeability and subsequent macular edema is a cardinal feature of early diabetic retinopathy (DR). Here, we investigated the role of bioactive lipid metabolites, in particular 12/15-lipoxygenase (LOX)-derived metabolites, in this process. LC/MS lipidomic screen of human retinal endothelial cells (HRECs) demonstrated that 15-HETE was the only significantly increased metabolite (2.4 ± 0.4-fold, P = 0.0004) by high glucose (30 mM) treatment. In the presence of arachidonic acid, additional eicosanoids generated by 12/15-LOX, including 12- and 11-HETEs, were significantly increased. Fluorescein angiography and retinal albumin leakage showed a significant decrease in retinal hyperpermeability in streptozotocin-induced diabetic mice lacking 12/15-LOX compared with diabetic WT mice. Our previous studies demonstrated the potential role of NADPH oxidase in mediating the permeability effect of 12- and 15-HETEs, therefore we tested the impact of intraocular injection of 12-HETE in mice lacking the catalytic subunit of NADPH oxidase (NOX2). The permeability effect of 12-HETE was significantly reduced in NOX2(-/-) mice compared with the WT mice. In vitro experiments also showed that 15-HETE induced HREC migration and tube formation in a NOX-dependent manner. Taken together our data suggest that 12/15-LOX is implicated in DR via a NOX-dependent mechanism.
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