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

Autor: Cornelis J.F. Van Noorden, Rutger P. van Heijningen, Ingeborg Klaassen, Anne-Eva van der Wijk, Paul Canning, Ilse M. C. Vogels, Reinier O. Schlingemann
Přispěvatelé: Medical Biology, AGEM - Endocrinology, metabolism and nutrition, ACS - Atherosclerosis & ischemic syndromes, AGEM - Digestive immunity, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Graduate School, Cell Biology and Histology, Ophthalmology, ACS - Microcirculation
Rok vydání: 2018
Předmět:
Zdroj: van der Wijk, A-E, Canning, P, van Heijningen, R P, Vogels, I M C, van Noorden, C J F, Klaassen, I & Schlingemann, R O 2019, ' Glucocorticoids exert differential effects on the endothelium in an in vitro model of the blood–retinal barrier ', Acta Ophthalmologica, vol. 97, no. 2, pp. 214-224 . https://doi.org/10.1111/aos.13909
Acta ophthalmologica, 97(2), 214-224. Copenhagen Scriptor
Acta Ophthalmologica, 97(2), 214-224. Wiley-Blackwell
ISSN: 1755-3768
1755-375X
Popis: Purpose: 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. Methods: 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. Results: 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. Conclusion: 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.
Databáze: OpenAIRE
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