title: High glucose alters retinal astrocytes phenotype through increased production of inflammatory cytokines and oxidative stress.
abstract: Astrocytes are macroglial cells that have a crucial role in development of the retinal vasculature and maintenance of the blood-retina-barrier (BRB). Diabetes affects the physiology and function of retinal vascular cells including astrocytes (AC) leading to breakdown of BRB. However, the detailed cellular mechanisms leading to retinal AC dysfunction under high glucose conditions remain unclear. Here we show that high glucose conditions did not induce the apoptosis of retinal AC, but instead increased their rate of DNA synthesis and adhesion to extracellular matrix proteins. These alterations were associated with changes in intracellular signaling pathways involved in cell survival, migration and proliferation. High glucose conditions also affected the expression of inflammatory cytokines in retinal AC, activated NF-κB, and prevented their network formation on Matrigel. In addition, we showed that the attenuation of retinal AC migration under high glucose conditions, and capillary morphogenesis of retinal endothelial cells on Matrigel, was mediated through increased oxidative stress. Antioxidant proteins including heme oxygenase-1 and peroxiredoxin-2 levels were also increased in retinal AC under high glucose conditions through nuclear localization of transcription factor nuclear factor-erythroid 2-related factor-2. Together our results demonstrated that high glucose conditions alter the function of retinal AC by increased production of inflammatory cytokines and oxidative stress with significant impact on their proliferation, adhesion, and migration.
authors: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.
authors: Eui Seok
authors: ES
authors: Shin
authors: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.
authors: Qiong
authors: Q
authors: Huang
authors: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.
authors: Zafer
authors: Z
authors: Gurel
authors: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.
authors: Christine M
authors: CM
authors: Sorenson
authors: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America; McPherson Eye Research Institute, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America.
authors: Nader
authors: N
authors: Sheibani
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004261:DNA Replication / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism*; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D012160:Retina / Q000166:cytology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000975:Antioxidants; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D018836:Inflammation Mediators; D016023:Integrins; D051267:NF-E2-Related Factor 2; D009419:Nerve Tissue Proteins; D010982:Platelet-Derived Growth Factor; C528900:glial fibrillary astrocytic protein, mouse; D005947:Glucose