Ameliorative effect of PACAP and VIP against increased permeability in a model of outer blood retinal barrier dysfunction

Scuderi, S; D'Amico, AG; Castorina, A; Imbesi, R; Carnazza, ML; D'Agata, V

Ameliorative effect of PACAP and VIP against increased permeability in a model of outer blood retinal barrier dysfunction

Scuderi, S D'Amico, AG Castorina, A

Imbesi, R Carnazza, ML D'Agata, V

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Publication Type:: Journal Article
Citation:: Peptides, 2013, 39 (1), pp. 119 - 124
Issue Date:: 2013-01-01

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Field	Value	Language
dc.contributor.author	Scuderi, S	en_US
dc.contributor.author	D'Amico, AG	en_US
dc.contributor.author	Castorina, A https://orcid.org/0000-0001-7037-759X	en_US
dc.contributor.author	Imbesi, R	en_US
dc.contributor.author	Carnazza, ML	en_US
dc.contributor.author	D'Agata, V	en_US
dc.date.available	2012-11-26	en_US
dc.date.issued	2013-01-01	en_US
dc.identifier.citation	Peptides, 2013, 39 (1), pp. 119 - 124	en_US
dc.identifier.issn	0196-9781	en_US
dc.identifier.uri	http://hdl.handle.net/10453/117117
dc.description.abstract	Breakdown of outer blood retinal barrier (BRB) due to the disruption of tight junctions (TJs) is one of the main factors accounting for diabetic macular edema (DME), a major complication of diabetic retinopathy. Previously it has been shown that PACAP and VIP are protective against several types of retinal injuries. However, their involvement in the maintenance of outer BRB function during DME remains uncovered. Here, using an in vitro model of DME, we explored the effects of both PACAP and VIP. Human retinal pigment epithelial cells (ARPE19) were cultured for 26 days either in normal glucose (5.5 mM, NG) or in high glucose (25 mM, HG). In addition, to mimic the inflammatory aspect of the diabetic milieu, cells were also treated with IL-1β (NG + IL-1β and HG + IL-1β). Effects of PACAP or VIP on cells permeability were evaluated by measuring both apical-to-basolateral movements of fluorescein isothyocyanate (FITC) dextran and transepithelial electrical resistance (TEER). Expression of TJ-related proteins was evaluated by immunoblot. Results demonstrated that NG + IL-1β and, to a greater extent, HG + IL-1β significantly increased FITC-dextran diffusion, paralleled by decreased TEER. PACAP or VIP reversed both of these effects. Furthermore, HG + IL-1β-induced reduction of claudin-1 and ZO-1 expression was reversed by PACAP and VIP. Occludin expression was not affected in any of the conditions tested. Altogether, these finding show that both peptides counteract HG + IL-1β-induced damage in ARPE19 cells, suggesting that they might be relevant to the maintenance of outer BRB function in DME. © 2012 Elsevier Inc.	en_US
dc.relation.ispartof	Peptides	en_US
dc.relation.isbasedon	10.1016/j.peptides.2012.11.015	en_US
dc.subject.classification	Endocrinology & Metabolism	en_US
dc.subject.mesh	Blood-Retinal Barrier	en_US
dc.subject.mesh	Cell Line	en_US
dc.subject.mesh	Tight Junctions	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Diabetes Complications	en_US
dc.subject.mesh	Fluorescein-5-isothiocyanate	en_US
dc.subject.mesh	Dextrans	en_US
dc.subject.mesh	Vasoactive Intestinal Peptide	en_US
dc.subject.mesh	Glucose	en_US
dc.subject.mesh	Gene Expression	en_US
dc.subject.mesh	Capillary Permeability	en_US
dc.subject.mesh	Electric Impedance	en_US
dc.subject.mesh	Pituitary Adenylate Cyclase-Activating Polypeptide	en_US
dc.subject.mesh	Interleukin-1beta	en_US
dc.subject.mesh	Macular Edema	en_US
dc.subject.mesh	Retinal Pigment Epithelium	en_US
dc.subject.mesh	Zonula Occludens-1 Protein	en_US
dc.subject.mesh	Claudin-1	en_US
dc.subject.mesh	Occludin	en_US
dc.title	Ameliorative effect of PACAP and VIP against increased permeability in a model of outer blood retinal barrier dysfunction	en_US
dc.type	Journal Article
utslib.citation.volume	1	en_US
utslib.citation.volume	39	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	0304 Medicinal and Biomolecular Chemistry	en_US
utslib.for	0606 Physiology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.issue	1	en_US
pubs.publication-status	Published	en_US
pubs.volume	39	en_US

Abstract:

Breakdown of outer blood retinal barrier (BRB) due to the disruption of tight junctions (TJs) is one of the main factors accounting for diabetic macular edema (DME), a major complication of diabetic retinopathy. Previously it has been shown that PACAP and VIP are protective against several types of retinal injuries. However, their involvement in the maintenance of outer BRB function during DME remains uncovered. Here, using an in vitro model of DME, we explored the effects of both PACAP and VIP. Human retinal pigment epithelial cells (ARPE19) were cultured for 26 days either in normal glucose (5.5 mM, NG) or in high glucose (25 mM, HG). In addition, to mimic the inflammatory aspect of the diabetic milieu, cells were also treated with IL-1β (NG + IL-1β and HG + IL-1β). Effects of PACAP or VIP on cells permeability were evaluated by measuring both apical-to-basolateral movements of fluorescein isothyocyanate (FITC) dextran and transepithelial electrical resistance (TEER). Expression of TJ-related proteins was evaluated by immunoblot. Results demonstrated that NG + IL-1β and, to a greater extent, HG + IL-1β significantly increased FITC-dextran diffusion, paralleled by decreased TEER. PACAP or VIP reversed both of these effects. Furthermore, HG + IL-1β-induced reduction of claudin-1 and ZO-1 expression was reversed by PACAP and VIP. Occludin expression was not affected in any of the conditions tested. Altogether, these finding show that both peptides counteract HG + IL-1β-induced damage in ARPE19 cells, suggesting that they might be relevant to the maintenance of outer BRB function in DME. © 2012 Elsevier Inc.

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http://hdl.handle.net/10453/117117