ArticleDiabetologia2013
Effects of modified LDL and HDL on retinal pigment epithelial cells: a role in diabetic retinopathy?
Article in Diabetologia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 81 citations in OpenAlex.
- Trial
- The role of glucagon-like peptide-1/GLP-1R and autophagy in diabetic cardiovascular disease.Pharmacological reports : PR · 2024Review
- Associations between lipid abnormalities and diabetic retinopathy across a large United States national database.Eye (London, England) · 2024Article
- The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease.Progress in retinal and eye research · 2024Review
- ABHD1 Facilitates Intermediate Filament-Mediated Endothelial Cell Chemotaxis by Regulating KRT1 and KRT2 in Diabetic Retinopathy.Journal of diabetes research · 2024Article
- Metabolic fingerprinting on retinal pigment epithelium thickness for individualized risk stratification of type 2 diabetes mellitus.Nature communications · 2023Article
- Synergism of mechanisms underlying early-stage changes in retina function in male hyperglycemic db/db mice in the absence and presence of chemically-induced dyslipidemia.Scientific reports · 2023Article
- Systemic Beta-Hydroxybutyrate Affects BDNF and Autophagy into the Retina of Diabetic Mice.International journal of molecular sciences · 2022Article
- The Effect of Hyperlipidemia on the Course of Diabetic Retinopathy-Literature Review.Journal of clinical medicine · 2022Review
- Aqueous Humor Apolipoprotein Concentration and Severity of Diabetic Retinopathy in Type 2 Diabetes.Mediators of inflammation · 2022Article
- MD2 blockade prevents modified LDL-induced retinal injury in diabetes by suppressing NADPH oxidase-4 interaction with Toll-like receptor-4.Experimental & molecular medicine · 2021Article
- Effects of modified lipoproteins on human trophoblast cells: a role in pre-eclampsia in pregnancies complicated by diabetes.BMJ open diabetes research & care · 2021Article
- Caffeine Protects Against Retinal Inflammation.Frontiers in pharmacology · 2021Article
- Role of glycolysis in retinal vascular endothelium, glia, pigment epithelium, and photoreceptor cells and as therapeutic targets for related retinal diseases.International journal of ophthalmology · 2021Review
- Autophagy: A Novel Pharmacological Target in Diabetic Retinopathy.Frontiers in pharmacology · 2021Review
- Protective or Harmful: The Dual Roles of Autophagy in Diabetic Retinopathy.Frontiers in medicine · 2021Review
- Metabolic Dysregulation and Neurovascular Dysfunction in Diabetic Retinopathy.Antioxidants (Basel, Switzerland) · 2020Review
- Effects of Modified Low-Density Lipoproteins and Fenofibrate on an Outer Blood-Retina Barrier Model: Implications for Diabetic Retinopathy.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2020Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
aims/hypothesisBlood-retina barrier leakage in diabetes results in extravasation of plasma lipoproteins. Intra-retinal modified LDLs have been implicated in diabetic retinopathy (DR), but their effects on retinal pigment epithelial (RPE) cells and the added effects of extravasated modified HDLs are unknown.
methodsIn human retinas from individuals with and without diabetes and DR, immunohistochemistry was used to detect ApoB, ApoA1 and endoplasmic reticulum (ER) stress markers. In cell culture, human RPE cells were treated with native LDL (N-LDL) or heavily-oxidised glycated LDL (HOG-LDL) with or without pretreatment with native HDL (N-HDL) or heavily-oxidised glycated HDL (HOG-HDL). Cell viability, oxidative stress, ER stress, apoptosis and autophagy were assessed by Cell Counting Kit-8 assay, dichlorofluorescein assay, western blotting, immunofluorescence and TUNEL assay. In separate experiments, RPE cells were treated with lipid oxidation products, 7-ketocholesterol (7-KC, 5-40 μmol/l) or 4-hydroxynonenal (4-HNE, 5-80 μmol/l), with or without pretreatment with N-HDL or HOG-HDL.
resultsApoB, ApoA1 staining and RPE ER stress were increased in the presence of DR. HOG-LDL but not N-LDL significantly decreased RPE cell viability and increased reactive oxygen species generation, ER stress, apoptosis and autophagy. Similarly, 4-HNE and 7-KC decreased viability and induced ER stress. Pretreatment with N-HDL mitigated these effects, whereas HOG-HDL was less effective by most, but not all, measures. CONCLUSIONS/
interpretationIn DR, extravascular modified LDL may promote RPE injury through oxidative stress, ER stress, autophagy and apoptosis. N-HDL has protective effects, but HOG-HDL is less effective. Extravasation and modification of HDL may modulate the injurious effects of extravasated modified LDL on the retinal pigment epithelium.
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