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- W3174689219 abstract "Blood-retinal barrier (BRB) is a biological unit composed of capillary endothelial cells and astrocytes, and its substantial apparatus is tight junction (TJ) between the endothelium. Since BRB is essential for maintaining the retinal microenvironment and low permeability, BRB breakdown is associated with diabetic retinopathy. However, the mechanisms inducing vascular leakage in diabetic retina remain to be fully clarified. While the glial cell line-derived neurotrophic factor (GDNF) was originally identified as a neurotrophic factor, our immunohistochemical studies show that GDNF is detected in the retinal astrocytes and GDNF receptor (GFR) alpha-1 is localized in the capillary endothelial cells comprising BRB. We also reveal that GDNF enhances the barrier function of TJs in endothelial cells. Several reports have demonstrated that various types of advanced glycation end-products (AGEs) are formed under hyperglycemic conditions such as diabetes in vivo. We next examined the effects of AGEs on astrocytes and endothelial cells. No types of AGE directly change the endothelial permeability, whereas glyceraldehyde-derived AGE (AGE2) acts on astrocytes to enhance the VEGF expression and conversely suppress the GDNF expression, causally promoting the vascular permeability of the BRB. Phenotypic transformation of astrocytes mediated by AGE2 is sufficient for significant increase of vascular leakage, and therefore may be involved in the pathogenesis of diabetic retinopathy." @default.
- W3174689219 created "2021-07-05" @default.
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- W3174689219 date "2006-03-01" @default.
- W3174689219 modified "2023-09-24" @default.
- W3174689219 title "Glial cell line‐derived neurotrophic factor (GDNF) regulates the vascular permeability of the blood‐retinal barrier (BRB)" @default.
- W3174689219 doi "https://doi.org/10.1096/fasebj.20.4.a636-d" @default.
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