Glucocorticoids exert differential effects on the endothelium in an in vitro model of the blood-retinal barrier.

Détails

ID Serval
serval:BIB_1B6B8974C00D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Glucocorticoids exert differential effects on the endothelium in an in vitro model of the blood-retinal barrier.
Périodique
Acta ophthalmologica
Auteur(s)
van der Wijk A.E., Canning P., van Heijningen R.P., Vogels IMC, van Noorden CJF, Klaassen I., Schlingemann R.O.
ISSN
1755-3768 (Electronic)
ISSN-L
1755-375X
Statut éditorial
Publié
Date de publication
03/2019
Peer-reviewed
Oui
Volume
97
Numéro
2
Pages
214-224
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Glucocorticoids (GCs) are used as treatment in diabetic macular oedema, a condition caused by blood-retinal barrier (BRB) disruption. The proposed mechanisms by which GCs reduce macular oedema are indirect anti-inflammatory effects and inhibition of VEGF production, but direct effects on the BRB endothelium may be equally important. Here, we investigated direct effects of GCs on the endothelium to understand the specific pathways of GC action, to enable development of novel therapeutics lacking the adverse side-effects of the presently used GCs.
Primary bovine retinal endothelial cells (BRECs) were grown on Transwell inserts and treated with hydrocortisone (HC), dexamethasone (Dex) or triamcinolone acetonide (TA). Molecular barrier integrity of the BRB was determined by mRNA and protein expression, and barrier function was assessed using permeability assays. In addition, we investigated whether TA was able to prevent barrier disruption after stimulation with VEGF or cytokines.
Treatment of BRECs with GCs resulted in upregulation of tight junction mRNA (claudin-5, occludin, ZO-1) and protein (claudin-5 and ZO-1). In functional assays, only TA strengthened the barrier function by reducing endothelial permeability. Moreover, TA was able to prevent cytokine-induced permeability in human retinal endothelial cells and VEGF-induced expression of plasmalemma vesicle-associated protein (PLVAP), a key player in VEGF-induced retinal vascular leakage.
Glucocorticoids have differential effects in an experimental in vitro BRB model. TA is the most potent in improving barrier function, both at the molecular and functional levels, and TA prevents VEGF-induced expression of PLVAP.
Mots-clé
Animals, Blood-Retinal Barrier/metabolism, Capillary Permeability, Cattle, Cells, Cultured, Disease Models, Animal, Endothelium, Vascular/drug effects, Endothelium, Vascular/metabolism, Endothelium, Vascular/pathology, Glucocorticoids/pharmacokinetics, Macular Edema/drug therapy, Macular Edema/metabolism, Macular Edema/pathology, Retinal Vessels/drug effects, Retinal Vessels/metabolism, Retinal Vessels/pathology, Tight Junctions, Triamcinolone Acetonide/pharmacokinetics, Vascular Endothelial Growth Factor A/biosynthesis, Vascular Endothelial Growth Factor A/drug effects, PLVAP, blood-retinal barrier, diabetic macular oedema, glucocorticoids, tight junctions
Pubmed
Web of science
Création de la notice
03/09/2018 11:41
Dernière modification de la notice
20/08/2019 12:52
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