ArticleInvestigative ophthalmology & visual science2012
Oxidative and endoplasmic reticulum stresses mediate apoptosis induced by modified LDL in human retinal Müller cells.
Article in Investigative ophthalmology & visual science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 66 citations in OpenAlex.
- Systemic strategies to prevent early diabetic retinopathy: targeting polyunsaturated fatty acid metabolism and eicosanoid signaling.Frontiers in medicine · 2026Review
- Single-cell RNA sequencing highlights a significant retinal Müller glial population in dry age-related macular degeneration.iScience · 2025Article
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- ABHD1 Facilitates Intermediate Filament-Mediated Endothelial Cell Chemotaxis by Regulating KRT1 and KRT2 in Diabetic Retinopathy.Journal of diabetes research · 2024Article
- The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease.Progress in retinal and eye research · 2024Review
- Endoplasmic reticulum stress: molecular mechanism and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Aldehyde Dehydrogenase and Aldo-Keto Reductase Enzymes: Basic Concepts and Emerging Roles in Diabetic Retinopathy.Antioxidants (Basel, Switzerland) · 2023Review
- Mustard gas exposure instigates retinal Müller cell gliosis.Experimental eye research · 2023Article
- Mechanisms of β-adrenergic receptors agonists in mediating pro and anti-apoptotic pathways in hyperglycemic Müller cells.Molecular biology reports · 2022Article
- Do different lipid components accelerate the pathogenesis and severity of Diabetic Retinopathy?International journal of retina and vitreous · 2022Article
- The Effect of Hyperlipidemia on the Course of Diabetic Retinopathy-Literature Review.Journal of clinical medicine · 2022Review
- Contribution of Müller Cells in the Diabetic Retinopathy Development: Focus on Oxidative Stress and Inflammation.Antioxidants (Basel, Switzerland) · 2022Review
- Apocynin ameliorates NADPH oxidase 4 (NOX4) induced oxidative damage in the hypoxic human retinal Müller cells and diabetic rat retina.Molecular and cellular biochemistry · 2021Article
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- Article
- Effects of modified lipoproteins on human trophoblast cells: a role in pre-eclampsia in pregnancies complicated by diabetes.BMJ open diabetes research & care · 2021Article
- 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
- The Role of Lipoxidation in the Pathogenesis of Diabetic Retinopathy.Frontiers in endocrinology · 2020Review
- Sphingosine Kinase-1 Is Essential for Maintaining External/Outer Limiting Membrane and Associated Adherens Junctions in the Aging Retina.Molecular neurobiology · 2019Article
- The unfolded protein response signaling and retinal Müller cell metabolism.Neural regeneration research · 2018Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
purposeWe previously showed that extravasated, modified LDL is implicated in pericyte loss in diabetic retinopathy (DR). Here, we investigate whether modified LDL induces apoptosis in retinal Müller glial cells.
methodsCultured human retinal Müller cells (MIO-M1) were treated with highly oxidized glycated LDL (HOG-LDL, 200 mg protein/L) or native LDL (N-LDL, 200 mg protein/L) for up to 24 hours with or without pretreatment with N-acetyl-cysteine (NAC, a blocker of oxidative stress) and 4-phenylbutyrate (4-PBA, a blocker of endoplasmic reticulum [ER] stress). Effects of HOG-LDL on cell viability, apoptosis, oxidative stress, and ER stress were assessed by cell viability, TUNEL, and Western blot assays. In separate experiments, Müller cells were treated with 7-ketocholesterol (7-KC, 5-20 μM) or 4-hydroxynonenal (4-HNE, 5-40 μM) for up to 24 hours. The same markers were measured.
resultsHOG-LDL induced apoptosis (decreased cell viability, increased TUNEL staining, increased expression of cleaved PARP, cleaved caspase-3, and BAX; decreased Bcl-2), oxidative stress (increased NOX4 and antioxidant enzymes, catalase, and superoxide dismutase 2), and ER stress (increased phospho-eIF2α, KDEL, ATF6, and CHOP). Pretreatment with NAC or 4-PBA partially attenuated apoptosis. In addition. NAC attenuated activation of ER stress. Similar to HOG-LDL, 7KC, and 4HNE also induced apoptosis, oxidative stress, and ER stress.
conclusionsOur data suggest that extravasated, modified lipoproteins may be implicated in apoptotic Müller cell death, acting at least partially via enhanced levels of oxidative and ER stresses. They support our main hypothesis that, in addition to hyperglycemia, extravasated and oxidized LDL is an important insult to the diabetic retina.
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