ArticleThe American journal of pathology2011
Microglia/macrophages migrate through retinal epithelium barrier by a transcellular route in diabetic retinopathy: role of PKCζ in the Goto Kakizaki rat model.
Article in The American journal of pathology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 1 of them a synthesis that pooled it.
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Who cites it
110 citing papers in PubMed, 1 synthesis or guideline pooled it, 219 citations in OpenAlex.
- Effects of diabetes on microglial physiology: a systematic review of in vitro, preclinical and clinical studies.Journal of neuroinflammation · 2023Pooled it
- Baseline morphological characteristics as predictors of final visual acuity in patients with branch retinal vein occlusions: MARVEL report no. 3.Indian journal of ophthalmology · 2018Trial
- Macrophage-Like Cell Density and Distribution in Relation to Vascular Leakage in Diabetes.Ophthalmology science · 2026Article
- 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
- Diabetic Retinopathy, a Comprehensive Overview on Pathophysiology and Relevant Experimental Models.International journal of molecular sciences · 2025Review
- Effects of VEGFA and ANGPT2 Antibodies on the Activation of Microglia in the Early Stages of Streptozotocin-Induced Pathogenesis of Diabetic Retinopathy.Genes to cells : devoted to molecular & cellular mechanisms · 2025Article
- Prospective evaluation of soluble CD14 as a biomarker following five aflibercept treatments in diabetic macular edema.Scientific reports · 2025Article
- Gut Microbes Secretions May Trigger Mononuclear Cell Migration and Offer Comorbidity Mechanism Between Inflammatory Bowel Disease and Diabetic Retinopathy.Mediators of inflammation · 2025Article
- TIN2 modulates FOXO1 mitochondrial shuttling to enhance oxidative stress-induced apoptosis in retinal pigment epithelium under hyperglycemia.Cell death and differentiation · 2024Article
- A new texture-based labeling framework for hyper-reflective foci identification in retinal optical coherence tomography images.Scientific reports · 2024Article
- Evidence for a Pro-Inflammatory State of Macrophages from Non-Obese Type-2 Diabetic Goto-Kakizaki Rats.International journal of molecular sciences · 2024Article
- Role of inflammation in a rat model of radiation retinopathy.Journal of neuroinflammation · 2024Article
- Deep Learning in Neovascular Age-Related Macular Degeneration.Medicina (Kaunas, Lithuania) · 2024Review
- Diabetes and high-glucose could upregulate the expression of receptor for activated C kinase 1 in retina.World journal of diabetes · 2024Article
- Caveolin-1 regulates inflammatory mediators in retinal endothelial cells.Molecular vision · 2024Article
- Effects of donor-specific microvascular anatomy on hemodynamic perfusion in human choriocapillaris.Scientific reports · 2023Article
- Metabolic fingerprinting on retinal pigment epithelium thickness for individualized risk stratification of type 2 diabetes mellitus.Nature communications · 2023Article
- Rodent Models of Diabetic Retinopathy as a Useful Research Tool to Study Neurovascular Cross-Talk.Biology · 2023Review
- Frontiers in diabetic retinal disease.Journal of diabetes and its complications · 2023Review
- Macrophage/microglia polarization for the treatment of diabetic retinopathy.Frontiers in endocrinology · 2023Review
50 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetic retinopathy is associated with ocular inflammation, leading to retinal barrier breakdown, macular edema, and visual cell loss. We investigated the molecular mechanisms involved in microglia/macrophages trafficking in the retina and the role of protein kinase Cζ (PKCζ) in this process. Goto Kakizaki (GK) rats, a model for spontaneous type 2 diabetes were studied until 12 months of hyperglycemia. Up to 5 months, sparse microglia/macrophages were detected in the subretinal space, together with numerous pores in retinal pigment epithelial (RPE) cells, allowing inflammatory cell traffic between the retina and choroid. Intercellular adhesion molecule-1 (ICAM-1), caveolin-1 (CAV-1), and PKCζ were identified at the pore border. At 12 months of hyperglycemia, the significant reduction of pores density in RPE cell layer was associated with microglia/macrophages accumulation in the subretinal space together with vacuolization of RPE cells and disorganization of photoreceptors outer segments. The intraocular injection of a PKCζ inhibitor at 12 months reduced iNOS expression in microglia/macrophages and inhibited their migration through the retina, preventing their subretinal accumulation. We show here that a physiological transcellular pathway takes place through RPE cells and contributes to microglia/macrophages retinal trafficking. Chronic hyperglycemia causes alteration of this pathway and subsequent subretinal accumulation of activated microglia/macrophages.
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