title: Retinal endothelial cells are more susceptible to oxidative stress and increased permeability than brain-derived endothelial cells.
abstract: Increased vascular permeability and oxidative stress are important in diabetic retinopathy. Because the cerebral microcirculation is much less affected in diabetes, our objectives are to compare: (1) glutathione peroxidase activity, (2) superoxide dismutase levels, (3) superoxide production, and (4) junctional protein (ZO-1) levels between retinal and brain-derived endothelial cells. Bovine brain and retinal endothelial cell cultures are incubated in medium containing either mM or 30 mM glucose for 5 days. Superoxide is measured in the medium and endothelial cells are then lysed and analyzed for glutathione peroxidase activity as well as levels of superoxide dismustase and ZO-1. The results demonstrate that, compared to brain-derived endothelial cells, retinal endothelial cells release high levels of superoxide, have less glutathione peroxidase activity and lower levels of superoxide dismutase, and ZO-1. Also, unlike brain-derived endothelial cells where ZO-1 levels increased in response to glucose, in retinal endothelial cells, ZO-1 levels are unaffected by glucose. These findings suggest that greater oxidative stress and lower junctional protein levels in retinal endothelial cells may contribute to blood/retinal barrier dysfunction in diabetic retinopathy.
authors.affiliation: Department of Pathology and the Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. paula-grammas@ouhsc.edu
authors.forename: Paula
authors.initials: P
authors.lastname: Grammas
authors.forename: Michael
authors.initials: M
authors.lastname: Riden
mesh_terms: D000818:Animals; D001813:Blood-Retinal Barrier / Q000502:physiology; D001921:Brain / Q000098:blood supply*; D002199:Capillary Permeability; D002417:Cattle; D002478:Cells, Cultured; D003930:Diabetic Retinopathy / Q000209:etiology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000378:metabolism; D012171:Retinal Vessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D062826:Zonula Occludens-1 Protein
chemical_list: D008565:Membrane Proteins; D010750:Phosphoproteins; D062826:Zonula Occludens-1 Protein; D013481:Superoxides; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005947:Glucose