ArticleGraefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie2021
A potential novel therapeutic target in diabetic retinopathy: a chemokine receptor (CCR2/CCR5) inhibitor reduces retinal vascular leakage in an animal model.
Article in Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Effects of diabetes on microglial physiology: a systematic review of in vitro, preclinical and clinical studies.Journal of neuroinflammation · 2023Pooled it
- Suboptimal Responses to Anti-VEGF in Retinal Neurovascular Diseases: Linking Aging and Alternative Angioinflammatory Pathways.Investigative ophthalmology & visual science · 2026Review
- Advances in the Role of the CD40-CD154 Pathway in the Pathogenesis of Diabetic Retinopathy.International journal of molecular sciences · 2026Review
- Overcoming host restrictions to enable continuous passaging of GII.3 human norovirus in human intestinal enteroids.Science advances · 2026Article
- Progress in the Cross-Organ Biomarker oxLDL in Promoting Pathological Neovascular Diseases.Antioxidants (Basel, Switzerland) · 2026Review
- Mechanistic Insights into the Combined Anti-inflammatory Effects of Bevacizumab and Triamcinolone in Hyperglycemic Retinal Cells: Modulation of MCP-1, CXCL10, and Their Receptors.Journal of ophthalmic & vision research · 2026Article
- Design and Synthesis of Fluorescence-Labeled TAK779 Analogs as Chemical Probes.Molecules (Basel, Switzerland) · 2025Article
- Heterotypic macrophages/microglia differentially contribute to retinal ischaemia and neovascularisation.Diabetologia · 2024Article
- Inflammation in diabetes complications: molecular mechanisms and therapeutic interventions.MedComm · 2024Review
- Ocular Vascular Diseases: From Retinal Immune Privilege to Inflammation.International journal of molecular sciences · 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
- Article
- Elucidating glial responses to products of diabetes-associated systemic dyshomeostasis.Progress in retinal and eye research · 2023Review
- CCR2-positive monocytes contribute to the pathogenesis of early diabetic retinopathy in mice.Diabetologia · 2023Article
- Naming the Barriers between Anti-CCR5 Therapy, Breast Cancer and Its Microenvironment.International journal of molecular sciences · 2022Review
- Diabetic Macular Edema: Current Understanding, Molecular Mechanisms and Therapeutic Implications.Cells · 2022Review
- The Chemokine Systems at the Crossroads of Inflammation and Energy Metabolism in the Development of Obesity.International journal of molecular sciences · 2021Review
- Nuclear factor of activated T-cells (NFAT) regulation of IL-1β-induced retinal vascular inflammation.Biochimica et biophysica acta. Molecular basis of disease · 2021Article
- Does C-C Motif Chemokine Ligand 2 (CCL2) Link Obesity to a Pro-Inflammatory State?International journal of molecular sciences · 2021Review
- Dysregulation of Leukocyte Trafficking in Type 2 Diabetes: Mechanisms and Potential Therapeutic Avenues.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
purposeWe have previously shown that the chemokine CCL2 plays an important role in monocyte trafficking into the retina and alteration of the BRB in an animal model of diabetic retinopathy. In this study, we examined the effect of pharmacologically targeting the chemokine pathway to reduce the increased retinal vascular permeability in this model.
methodsC57BL/6 J mice were made diabetic using streptozotocin. After 4 months of diabetes, mice (n = 10) were treated by intraperitoneal injections of TAK-779 (dual CCR2/CCR5 inhibitor) (30 mg/kg) daily for 2 weeks. Retinal vascular permeability and protein expression were done using western blot. The SDF-1 levels were measured by ELISA. Immune cell infiltration in the retinas was measured using flow cytometry.
resultsThe dual inhibitor significantly decreased retinal vascular permeability in diabetic animals. There was a significant reduction in macrophage/microglia infiltration in the retinas of treated animals. Levels of SDF-1 and ICAM-1 were significantly reduced and the tight junction protein ZO-1 level was increased, and phospho-VE-Cad was significantly reduced with drug treatment.
conclusionsA chemokine receptor inhibitor (CCR2/CCR5) can reduce retinal vascular permeability in diabetic animals. Targeting the chemokine pathway pharmacologically may be used as a novel therapeutic strategy in management of diabetic macular edema.
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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.