ArticleDiabetologia2016
Survival or death: a dual role for autophagy in stress-induced pericyte loss in diabetic retinopathy.
Article in Diabetologia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 118 citations in OpenAlex.
- Dysfunction of the Neurovascular Unit in Diabetic Retinopathy: Advances from Molecular Mechanisms to Targeted Interventions.Stem cell reviews and reports · 2026Review
- Stage-Associated Cellular and Molecular Signatures in Diabetic Retinopathy Identified Through Integrated Bulk and Single-Cell Transcriptomic Analysis.International journal of molecular sciences · 2026Article
- Molecular stress and neurovascular injury in the diabetic retina.The Journal of clinical investigation · 2026Review
- Exploring Vitamin D Signaling-Associated Biomarkers and Their Diagnostic Value in Diabetic Retinopathy: A Combined Transcriptomic and Single-Cell Analysis With Experimental Validation.Journal of diabetes research · 2026Article
- Autophagy in ocular diseases: from mechanisms to therapeutic potential.Frontiers in cell and developmental biology · 2026Review
- Dual regulation of autophagy: paradoxical effects on tumor angiogenesis.Frontiers in cell and developmental biology · 2026Review
- MAPK8 and HDAC6: potential biomarkers related to autophagy in diabetic retinopathy based on bioinformatics analysis.Frontiers in endocrinology · 2025Article
- Research progress on Nrf2 intervention in the treatment of diabetic retinopathy.Frontiers in endocrinology · 2025Review
- The role of glucagon-like peptide-1/GLP-1R and autophagy in diabetic cardiovascular disease.Pharmacological reports : PR · 2024Review
- Diabetic Retinopathy: New Treatment Approaches Targeting Redox and Immune Mechanisms.Antioxidants (Basel, Switzerland) · 2024Review
- Asiaticoside Attenuates Blood-Spinal Cord Barrier Disruption by Inhibiting Endoplasmic Reticulum Stress in Pericytes After Spinal Cord Injury.Molecular neurobiology · 2024Article
- Role of autophagy in angiogenic potential of vascular pericytes.Frontiers in cell and developmental biology · 2024Review
- 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
- Circulating Sphingolipids in Insulin Resistance, Diabetes and Associated Complications.International journal of molecular sciences · 2023Review
- The Role of Non-coding RNAs in Methamphetamine-Induced Neurotoxicity.Cellular and molecular neurobiology · 2023Review
- Thioredoxin1 is a target to attenuate diabetes‑induced RPE cell dysfunction in human ARPE19 cells by alleviating oxidative stress.Molecular medicine reports · 2023Article
- Three Major Causes of Metabolic Retinal Degenerations and Three Ways to Avoid Them.International journal of molecular sciences · 2023Review
- Autophagy in the retinal neurovascular unit: New perspectives into diabetic retinopathy.Journal of diabetes · 2023Review
- The ideal treatment timing for diabetic retinopathy: the molecular pathological mechanisms underlying early-stage diabetic retinopathy are a matter of concern.Frontiers in endocrinology · 2023Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
aims/hypothesisIntra-retinal extravasation and modification of LDL have been implicated in diabetic retinopathy: autophagy may mediate these effects.
methodsImmunohistochemistry was used to detect autophagy marker LC3B in human and murine diabetic and non-diabetic retinas. Cultured human retinal capillary pericytes (HRCPs) were treated with in vitro-modified heavily-oxidised glycated LDL (HOG-LDL) vs native LDL (N-LDL) with or without autophagy modulators: green fluorescent protein-LC3 transfection; small interfering RNAs against Beclin-1, c-Jun NH(2)-terminal kinase (JNK) and C/EBP-homologous protein (CHOP); autophagy inhibitor 3-MA (5 mmol/l) and/or caspase inhibitor Z-VAD-fmk (100 μmol/l). Autophagy, cell viability, oxidative stress, endoplasmic reticulum stress, JNK activation, apoptosis and CHOP expression were assessed by western blots, CCK-8 assay and TUNEL assay. Finally, HOG-LDL vs N-LDL were injected intravitreally to STZ-induced diabetic vs control rats (yielding 50 and 200 mg protein/l intravitreal concentration) and, after 7 days, retinas were analysed for ER stress, autophagy and apoptosis.
resultsIntra-retinal autophagy (LC3B staining) was increased in diabetic vs non-diabetic humans and mice. In HRCPs, 50 mg/l HOG-LDL elicited autophagy without altering cell viability, and inhibition of autophagy decreased survival. At 100-200 mg/l, HOG-LDL caused significant cell death, and inhibition of either autophagy or apoptosis improved survival. Further, 25-200 mg/l HOG-LDL dose-dependently induced oxidative and ER stress. JNK activation was implicated in autophagy but not in apoptosis. In diabetic rat retina, 50 mg/l intravitreal HOG-LDL elicited autophagy and ER stress but not apoptosis; 200 mg/l elicited greater ER stress and apoptosis.
conclusionsAutophagy has a dual role in diabetic retinopathy: under mild stress (50 mg/l HOG-LDL) it is protective; under more severe stress (200 mg/l HOG-LDL) it promotes cell death.
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Registered trials
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