title: Dexamethasone reverses the effects of high glucose on human retinal endothelial cell permeability and proliferation in vitro.
abstract: Diabetic macular oedema (DMO), a leading cause of preventable visual loss in the working population, is caused by an increase in microvascular endothelial cell permeability, and its prevalence is on the increase in parallel with the rising worldwide prevalence of diabetes. It is known that retinal vascular leakage in DMO is contributed to by VEGF upregulation as well as non-VEGF dependent inflammatory pathways, and the potential use of anti-inflammatory agents such as the glucocorticoids, including dexamethasone are being extensively studied. However, the mechanisms of action of dexamethasone in DMO reduction are not fully understood. Using human primary retinal endothelial cells (REC) the in vitro effect of dexamethasone in modulating the proliferation, permeability and gene expression of key tight and adheren junction components, and the expression of angiopoietins (Ang) 1 and 2 in high (25 mM) glucose conditions were investigated. High glucose decreased REC proliferation, an effect that was reversed by dexamethasone. High glucose conditions significantly increased REC permeability and decreased claudin-5, occludin and JAM-A gene expression; dexamethasone was effective in partially reversing these changes, restoring EC permeability to the normal or near normal state. High glucose levels resulted in reduction of Ang1 secretion, although Ang2 levels were consistently high. DEX increased Ang1 and decreased Ang2, indicating that the balance of Ang1/Ang2 may be important in determining functional changes in REC under high glucose conditions.
authors: University of Nottingham, Academic Ophthalmology, Division of Clinical Neuroscience, B Floor, Eye and ENT Building, Queen's Medical Centre, Nottingham, NG7 2UH, UK. Electronic address: E.stewart@nottingham.ac.uk.
authors: E A
authors: EA
authors: Stewart
authors: University of Nottingham, Academic Ophthalmology, Division of Clinical Neuroscience, B Floor, Eye and ENT Building, Queen's Medical Centre, Nottingham, NG7 2UH, UK. Electronic address: msxss1@nottingham.ac.uk.
authors: S
authors: S
authors: Saker
authors: University of Nottingham, Academic Ophthalmology, Division of Clinical Neuroscience, B Floor, Eye and ENT Building, Queen's Medical Centre, Nottingham, NG7 2UH, UK. Electronic address: wma@nottingham.ac.uk.
authors: W M
authors: WM
authors: Amoaku
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D002463:Cell Membrane Permeability / Q000187:drug effects*; D049109:Cell Proliferation; D002478:Cells, Cultured; D062507:Claudin-5 / Q000096:biosynthesis / Q000235:genetics; D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage / Q000493:pharmacokinetics; D005947:Glucose / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008269:Macular Edema / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012313:RNA / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D012160:Retina / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D013549:Sweetening Agents / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D015815:Cell Adhesion Molecules; D062507:Claudin-5; C407243:F11R protein, human; D005938:Glucocorticoids; D011956:Receptors, Cell Surface; D013549:Sweetening Agents; D012313:RNA; D003907:Dexamethasone; C046366:angiogenin; D012259:Ribonuclease, Pancreatic; D005947:Glucose
keywords: Angiopoietin; Dexamethasone; Diabetic macular oedema; Diabetic retinopathy; Endothelial permeability; Tight junction