ArticleDiabetologia2021
Erythropoietin protects the inner blood-retinal barrier by inhibiting microglia phagocytosis via Src/Akt/cofilin signalling in experimental diabetic retinopathy.
Article in Diabetologia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
55 citing papers in PubMed, 2 syntheses or guidelines pooled it, 89 citations in OpenAlex.
- Exploring the role of oxidative stress in retinal vein occlusion: an updated and comprehensive review on the pathophysiology and treatment perspectives.International ophthalmology · 2025Pooled it
- Effects of diabetes on microglial physiology: a systematic review of in vitro, preclinical and clinical studies.Journal of neuroinflammation · 2023Pooled it
- Artesunate ameliorates experimental autoimmune uveitis by inhibiting the LCN2-STAT3 axis and suppressing microglial activation.Redox report : communications in free radical research · 2026Article
- Microglial TSPAN4-Dependent Migrasomes Promote Pathological Retinal Neovascularization via Immune-Vascular Crosstalk.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Circular RNA circPSEN1 promotes neovascularization by regulating the miR-150-5p/TRIM65 axis in diabetic retinopathy.Biochemistry and biophysics reports · 2026Article
- Unveiling a unique microglial phenotype promoting oxidation in the iBRB: insights from single-cell transcriptomics in the NPDR rat model.Cell & bioscience · 2026Article
- AMPAR dysregulation in microglia drives vascular pathology in diabetic retinopathy via the P2X7R/NLRP3/IL-1β pathway.Journal of translational medicine · 2026Article
- Hepatotoxic Mechanisms of Polyethylene Terephthalate Microplastics Revealed by Network Toxicology, Molecular Docking, and In Vivo Validation.International journal of molecular sciences · 2026Article
- Microglial polarization in retinal neovascularization: Friend or foe?Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- Chronic dental lighting disrupts blood-retinal barrier homeostasis via vascular and inflammatory pathways.International journal of oral science · 2026Article
- Review: The role of microglia in diabetic retinopathy and its potential as a therapeutic target.Molecular vision · 2026Review
- Warfarin and bevacizumab suppress tumor progression in pancreatic ductal adenocarcinoma by targeting EGFR-PI3K-Akt signaling: inhibition of proliferation/migration and apoptosis induction.Translational cancer research · 2025Article
- Hyperglycemia impairs microglia responding to retinal vasculopathy via enhanced norepinephrine-ADRB2 signaling.Journal of neuroinflammation · 2025Article
- The blood-retinal barrier in ocular pathologies: an updated narrative review.International ophthalmology · 2025Review
- Mechanisms of action of retinal microglia in diabetic retinopathy (Review).International journal of molecular medicine · 2025Review
- Pharmacovigilance analysis of vision disorders relating to brimonidine treatment and mechanism study using network toxicology and molecular docking.Scientific reports · 2025Article
- Shifting of the local inflammatory characteristics of diabetic macular edema manifested in SD-OCT after anti-VEGF treatment and associations with system inflammatory bioparameters.Scientific reports · 2025Article
- Advances in Modeling the Inner Blood-Retinal Barrier: From Static Tissue Cell Cultures to Microphysiological Systems.Pharmaceuticals (Basel, Switzerland) · 2025Review
- IKZF3 promotes gastric cancer progression via Hedgehog signaling activation and is targetable by SANT-1.Acta biochimica et biophysica Sinica · 2025Article
- High-resolution multimodal visible light optical coherence tomography and scanning laser ophthalmoscopy forBiomedical optics express · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisMicroglial activation in diabetic retinopathy and the protective effect of erythropoietin (EPO) have been extensively studied. However, the regulation of microglia in the retina and its relationship to inner blood-retinal barrier (iBRB) maintenance have not been fully characterised. In this study, we investigated the role of microglia in iBRB breakdown in diabetic retinopathy and the protective effects of EPO in this context.
methodsMale Sprague Dawley rats were injected intraperitoneally with streptozotocin (STZ) to establish the experimental model of diabetes. At 2 h after STZ injection, the right and left eyes were injected intravitreally with EPO (16 mU/eye, 2 μl) and an equivalent volume of normal saline (NaCl 154 mmol/l), respectively. The rats were killed at 2 or 8 weeks after diabetes onset. Microglia activation was detected by ionised calcium binding adaptor molecule (IBA)-1 immunolabelling. Leakage of the iBRB was evaluated by albumin staining and FITC-dextran permeability assay. BV
resultsIn diabetic rat retinas, phagocytosis of endothelial cells by activated microglia was observed at 8 weeks, resulting in an increased number of acellular capillaries (increased by 426.5%) and albumin leakage. Under hypoxic conditions, activated microglia transmigrated to the opposite membrane of the transwell, where they disrupted the endothelial cell monolayer by engulfing endothelial cells. The activation and phagocytic activity of microglia was blocked by intravitreal injection of EPO. In vitro, IBA-1, CD11b and C1r protein levels were increased by 50.9%, 170.0% and 135.5%, respectively, by hypoxia, whereas the phosphorylated proteins of Src/Akt/cofilin signalling pathway components were decreased by 74.2%, 47.8% and 39.7%, respectively, compared with the control; EPO treatment abrogated these changes. CONCLUSIONS/
interpretationIn experimental diabetic retinopathy, activated microglia penetrate the basement membrane of the iBRB and engulf endothelial cells, leading to iBRB breakdown. EPO exerts a protective effect that preserves iBRB integrity via activation of Src/Akt/cofilin signalling in microglia, as demonstrated in vitro. These data support a causal role for activated microglia in iBRB breakdown and highlight the therapeutic potential of EPO for the treatment of diabetic retinopathy. Graphical abstract.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.