ArticleInvestigative ophthalmology & visual science2023
CD40 Upregulation in the Retina of Patients With Diabetic Retinopathy: Association With TRAF2/TRAF6 Upregulation and Inflammatory Molecule Expression.
Article in Investigative ophthalmology & visual science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 11 citations in OpenAlex.
- Advances in the Role of the CD40-CD154 Pathway in the Pathogenesis of Diabetic Retinopathy.International journal of molecular sciences · 2026Review
- AAV2.7m8 transduction of stage 2 human retinal organoids induces highly variable responses in innate and inflammatory gene expression and cytokine secretion.Experimental eye research · 2025Article
- Effects of Treadmill Exercise on Retinal Vascular Morphology, Function, and Circulating Immune Factors in a Mouse Model of Retinal Degeneration.Investigative ophthalmology & visual science · 2025Article
- Liquid Biopsy Combined with Multi-Omics Approaches in Diagnosis, Management, and Progression of Diabetic Retinopathy.Biomedicines · 2025Review
- CD40 Induces Unfolded Protein Response, Upregulation of VEGF, and Vascular Leakage in Diabetic Retinopathy.Diabetes · 2025Article
- Identifying therapeutic target genes for diabetic retinopathy using systematic druggable genome-wide Mendelian randomization.Diabetology & metabolic syndrome · 2025Article
- Research on interdisciplinary measurement and evolutionary path in the field of ophthalmology.Frontiers in ophthalmology · 2025Article
- Role of inflammatory signaling pathways involving the CD40-CD40L-TRAF cascade in diabetes and hypertension-insights from animal and human studies.Basic research in cardiology · 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
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Purpose: CD40 is upregulated in the retinas of diabetic mice, drives pro-inflammatory molecule expression, and promotes diabetic retinopathy. The role of CD40 in diabetic retinopathy in humans is unknown. Upregulation of CD40 and its downstream signaling molecules TNF receptor associated factors (TRAFs) is a key feature of CD40-driven inflammatory disorders. We examined the expression of CD40, TRAF2, and TRAF6 as well as pro-inflammatory molecules in retinas from patients with diabetic retinopathy. Methods: Posterior poles from patients with diabetic retinopathy and non-diabetic controls were stained with antibodies against von Willebrand factor (labels endothelial cells), cellular retinaldehyde-binding protein (CRALBP), or vimentin (both label Müller cells) plus antibodies against CD40, TRAF2, TRAF6, ICAM-1, CCL2, TNF-α, and/or phospho-Tyr783 phospholipase Cγ1 (PLCγ1). Sections were analyzed by confocal microscopy. Results: CD40 expression was increased in endothelial and Müller cells from patients with diabetic retinopathy. CD40 was co-expressed with ICAM-1 in endothelial cells and with CCL2 in Müller cells. TNF-α was detected in retinal cells from these patients, but these cells lacked endothelial/Müller cell markers. CD40 in Müller cells from patients with diabetic retinopathy co-expressed activated phospholipase Cγ1, a molecule that induces TNF-α expression in myeloid cells in mice. CD40 upregulation in endothelial cells and Müller cells from patients with diabetic retinopathy was accompanied by TRAF2 and TRAF6 upregulation. Conclusions: CD40, TRAF2, and TRAF6 are upregulated in patients with diabetic retinopathy. CD40 associates with expression of pro-inflammatory molecules. These findings suggest that CD40-TRAF signaling may promote pro-inflammatory responses in the retinas of patients with diabetic retinopathy.
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