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

Acta Ophthalmologica
Anne-Eva van der WijkReinier O Schlingemann

Abstract

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 wa...Continue Reading

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