ArticleDiabetologia2022
Disruption of retinal inflammation and the development of diabetic retinopathy in mice by a CD40-derived peptide or mutation of CD40 in Müller cells.
Article in Diabetologia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Advances in the Role of the CD40-CD154 Pathway in the Pathogenesis of Diabetic Retinopathy.International journal of molecular sciences · 2026Review
- Effects of New P2X7R Antagonists on Retinal Inflammatory Degenerative Conditions.Inflammation · 2026Article
- Evaluating Systemic Immune-Inflammation Index and Mortality in Diabetic Retinopathy: A NHANES 2005-2018 Cohort Study.Ophthalmology and therapy · 2026Article
- Targeting the gut-retina axis: mechanistic insights and therapeutic prospects for diabetic retinopathy.Inflammopharmacology · 2025Review
- Crosstalk Between Neuronal and Glial Cells in Diabetic Retinopathy: Mechanisms and Implications for Neurodegeneration.Molecular neurobiology · 2025Review
- Characterization of tertiary lymphoid structure identifies competitive binding of CD40 and STING with TRAF2 driving IRF4-mediated B cell activation in esophageal squamous cell carcinoma.Cancer gene therapy · 2025Article
- CD40 Induces Unfolded Protein Response, Upregulation of VEGF, and Vascular Leakage in Diabetic Retinopathy.Diabetes · 2025Article
- Exploring the correlations between six serological inflammatory markers and different stages of type 2 diabetic retinopathy.Scientific reports · 2025Article
- Methylglyoxal: A Key Factor for Diabetic Retinopathy and Its Effects on Retinal Damage.Biomedicines · 2024Review
- Raddeanin A Protects the BRB Through Inhibiting Inflammation and Apoptosis in the Retina of Alzheimer's Disease.Neurochemical research · 2024Article
- Causal Effects of Oxidative Stress on Diabetes Mellitus and Microvascular Complications: Insights Integrating Genome-Wide Mendelian Randomization, DNA Methylation, and Proteome.Antioxidants (Basel, Switzerland) · 2024Article
- Investigation of the Systemic Immune Inflammation (SII) Index as an Indicator of Morbidity and Mortality in Type 2 Diabetic Retinopathy Patients in a 4-Year Follow-Up Period.Medicina (Kaunas, Lithuania) · 2024Article
- Article
- SRY-box transcription factor 9 modulates Müller cell gliosis in diabetic retinopathy by upregulating TXNIP transcription.Experimental animals · 2023Article
- The Role of Müller Cells in Diabetic Macular Edema.Investigative ophthalmology & visual science · 2023Review
- CD40 Upregulation in the Retina of Patients With Diabetic Retinopathy: Association With TRAF2/TRAF6 Upregulation and Inflammatory Molecule Expression.Investigative ophthalmology & visual science · 2023Article
- Diabetic vascular diseases: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2023Review
- Exploring the Correlation Between the Systemic Immune Inflammation Index (SII), Systemic Inflammatory Response Index (SIRI), and Type 2 Diabetic Retinopathy.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Article
- 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
- The role of retinal Müller cells in diabetic retinopathy and related therapeutic advances.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
aims/hypothesisCD40 expressed in Müller cells is a central driver of diabetic retinopathy. CD40 causes phospholipase Cγ1 (PLCγ1)-dependent ATP release in Müller cells followed by purinergic receptor (P2X
methodsB6 and transgenic mice with Müller cell-restricted expression of wild-type (WT) CD40 or CD40 with mutations in TNF receptor-associated factor (TRAF) binding sites were made diabetic using streptozotocin. Leucostasis was assessed using FITC-conjugated concanavalin A. Histopathology was examined in the retinal vasculature. Expression of inflammatory molecules and phospho-Tyr783 PLCγ1 (p-PLCγ1) were assessed using real-time PCR, immunoblot and/or immunohistochemistry. Release of ATP and cytokines were measured by ATP bioluminescence and ELISA, respectively.
resultsHuman Müller cells with CD40 ΔT2,3 (lacks TRAF2,3 binding sites) were unable to phosphorylate PLCγ1 and release ATP in response to CD40 ligation, and could not induce TNF-α/IL-1β secretion in bystander myeloid cells. CD40-TRAF signalling acted via Src to induce PLCγ1 phosphorylation. Diabetic mice in which WT CD40 in Müller cells was replaced by CD40 ΔT2,3 failed to exhibit phosphorylation of PLCγ1 in these cells and upregulate P2X CONCLUSIONS/
interpretationCD40-TRAF2,3 signalling activated the CD40-PLCγ1-ATP-P2X
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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.