ArticleDiabetologia2014
CD40 promotes the development of early diabetic retinopathy in mice.
Article in Diabetologia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Effects of diabetes on microglial physiology: a systematic review of in vitro, preclinical and clinical studies.Journal of neuroinflammation · 2023Pooled it
- Advances in the Role of the CD40-CD154 Pathway in the Pathogenesis of Diabetic Retinopathy.International journal of molecular sciences · 2026Review
- Sex Differences in Inflammatory Plasma Proteins in Patients With Diabetic Retinopathy.Translational vision science & technology · 2025Article
- CD40 Induces Unfolded Protein Response, Upregulation of VEGF, and Vascular Leakage in Diabetic Retinopathy.Diabetes · 2025Article
- Global trends and hotspots of inflammation in diabetic retinopathy: a literature review and bibliometric analysis.Frontiers in medicine · 2025Review
- Induction, amplification, and propagation of diabetic retinopathy-associated inflammatory cytokines between human retinal microvascular endothelial and Müller cells and in the mouse retina.Cellular signalling · 2024Article
- Müller Glia Co-Regulate Barrier Permeability with Endothelial Cells in an Vitro Model of Hyperglycemia.International journal of molecular sciences · 2024Article
- Role of exosome-derived miRNAs in diabetic wound angiogenesis.Molecular and cellular biochemistry · 2024Review
- Inflammation in diabetes complications: molecular mechanisms and therapeutic interventions.MedComm · 2024Review
- Article
- CCR1 mediates Müller cell activation and photoreceptor cell death in macular and retinal degeneration.eLife · 2023Article
- CD40 Ligand-CD40 Interaction Is an Intermediary between Inflammation and Angiogenesis in Proliferative Diabetic Retinopathy.International journal of molecular sciences · 2023Article
- Pediatric Type 1 Diabetes: Mechanisms and Impact of Technologies on Comorbidities and Life Expectancy.International journal of molecular sciences · 2023Review
- 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
- Elucidating glial responses to products of diabetes-associated systemic dyshomeostasis.Progress in retinal and eye research · 2023Review
- Hyperglycemia Promotes Mitophagy and Thereby Mitigates Hyperglycemia-Induced Damage.The American journal of pathology · 2022Article
- Disruption of retinal inflammation and the development of diabetic retinopathy in mice by a CD40-derived peptide or mutation of CD40 in Müller cells.Diabetologia · 2022Article
- Ferroptosis: a double-edged sword mediating immune tolerance of cancer.Cell death & disease · 2022Review
- Regulations of Retinal Inflammation: Focusing on Müller Glia.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
aims/hypothesisMicroangiopathy is a leading complication of diabetes that commonly affects the retina. Degenerate capillaries are a central feature of diabetic retinopathy. An inflammatory process has been linked to the development of diabetic retinopathy but its regulation is incompletely understood. Cluster of differentiation (CD) 40 is a member of the TNF receptor superfamily that promotes the development of certain inflammatory disorders. The role of CD40 in diabetic microangiopathy is unknown.
methodsB6 and Cd40−/− mice were administered streptozotocin to induce diabetes. Leucostasis was assessed using fluorescein isothiocyanate-conjugated concanavalin A. Retinal Icam1 and Cd40 mRNA levels were examined using real-time PCR. Protein nitration was assessed by immunohistochemistry. Histopathology was examined in the retinal vasculature. CD40 expression was assessed by flow cytometry and immunohistochemistry. Intercellular adhesion molecule 1 (ICAM-1) and nitric oxide synthase 2 (NOS2) were examined by immunoblot and/or flow cytometry. Nitric oxide production was examined by immunoblot and Griess reaction.
resultsIn mouse models of diabetes, Cd40−/− mice exhibited reduced retinal leucostasis and did not develop capillary degeneration in comparison with B6 mice. Diabetic Cd40−/− mice had diminished ICAM-1 upregulation and decreased protein nitration. Cd40 mRNA levels were increased in the retinas of diabetic B6 mice compared with non-diabetic controls. CD40 expression increased in retinal Müller cells, endothelial cells and microglia of diabetic animals. CD40 stimulation upregulated ICAM-1 in retinal endothelial cells and Müller cells. CD40 ligation upregulated NOS2 and nitric oxide production by Müller cells. CONCLUSIONS/
interpretationCD40-deficient mice were protected fromthe development of diabetic retinopathy. These mice exhibited diminished inflammatory responses linked to diabetic retinopathy. CD40 stimulation of retinal cells triggered these pro-inflammatory responses.
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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.