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A New Human Blood–Retinal Barrier Model Based on Endothelial Cells, Pericytes, and Astrocytes

Blood–retinal barrier (BRB) dysfunction represents one of the most significant changes occurring during diabetic retinopathy. We set up a high-reproducible human-based in vitro BRB model using retinal pericytes, retinal astrocytes, and retinal endothelial cells in order to replicate the human in viv...

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Autores principales: Fresta, Claudia G., Fidilio, Annamaria, Caruso, Giuseppe, Caraci, Filippo, Giblin, Frank J., Marco Leggio, Gian, Salomone, Salvatore, Drago, Filippo, Bucolo, Claudio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084779/
https://www.ncbi.nlm.nih.gov/pubmed/32121029
http://dx.doi.org/10.3390/ijms21051636
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author Fresta, Claudia G.
Fidilio, Annamaria
Caruso, Giuseppe
Caraci, Filippo
Giblin, Frank J.
Marco Leggio, Gian
Salomone, Salvatore
Drago, Filippo
Bucolo, Claudio
author_facet Fresta, Claudia G.
Fidilio, Annamaria
Caruso, Giuseppe
Caraci, Filippo
Giblin, Frank J.
Marco Leggio, Gian
Salomone, Salvatore
Drago, Filippo
Bucolo, Claudio
author_sort Fresta, Claudia G.
collection PubMed
description Blood–retinal barrier (BRB) dysfunction represents one of the most significant changes occurring during diabetic retinopathy. We set up a high-reproducible human-based in vitro BRB model using retinal pericytes, retinal astrocytes, and retinal endothelial cells in order to replicate the human in vivo environment with the same numerical ratio and layer order. Our findings showed that high glucose exposure elicited BRB breakdown, enhanced permeability, and reduced the levels of junction proteins such as ZO-1 and VE-cadherin. Furthermore, an increased expression of pro-inflammatory mediators (IL-1β, IL-6) and oxidative stress-related enzymes (iNOS, Nox2) along with an increased production of reactive oxygen species were observed in our triple co-culture paradigm. Finally, we found an activation of immune response-regulating signaling pathways (Nrf2 and HO-1). In conclusion, the present model mimics the closest human in vivo milieu, providing a valuable tool to study the impact of high glucose in the retina and to develop novel molecules with potential effect on diabetic retinopathy.
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spelling pubmed-70847792020-03-24 A New Human Blood–Retinal Barrier Model Based on Endothelial Cells, Pericytes, and Astrocytes Fresta, Claudia G. Fidilio, Annamaria Caruso, Giuseppe Caraci, Filippo Giblin, Frank J. Marco Leggio, Gian Salomone, Salvatore Drago, Filippo Bucolo, Claudio Int J Mol Sci Article Blood–retinal barrier (BRB) dysfunction represents one of the most significant changes occurring during diabetic retinopathy. We set up a high-reproducible human-based in vitro BRB model using retinal pericytes, retinal astrocytes, and retinal endothelial cells in order to replicate the human in vivo environment with the same numerical ratio and layer order. Our findings showed that high glucose exposure elicited BRB breakdown, enhanced permeability, and reduced the levels of junction proteins such as ZO-1 and VE-cadherin. Furthermore, an increased expression of pro-inflammatory mediators (IL-1β, IL-6) and oxidative stress-related enzymes (iNOS, Nox2) along with an increased production of reactive oxygen species were observed in our triple co-culture paradigm. Finally, we found an activation of immune response-regulating signaling pathways (Nrf2 and HO-1). In conclusion, the present model mimics the closest human in vivo milieu, providing a valuable tool to study the impact of high glucose in the retina and to develop novel molecules with potential effect on diabetic retinopathy. MDPI 2020-02-27 /pmc/articles/PMC7084779/ /pubmed/32121029 http://dx.doi.org/10.3390/ijms21051636 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fresta, Claudia G.
Fidilio, Annamaria
Caruso, Giuseppe
Caraci, Filippo
Giblin, Frank J.
Marco Leggio, Gian
Salomone, Salvatore
Drago, Filippo
Bucolo, Claudio
A New Human Blood–Retinal Barrier Model Based on Endothelial Cells, Pericytes, and Astrocytes
title A New Human Blood–Retinal Barrier Model Based on Endothelial Cells, Pericytes, and Astrocytes
title_full A New Human Blood–Retinal Barrier Model Based on Endothelial Cells, Pericytes, and Astrocytes
title_fullStr A New Human Blood–Retinal Barrier Model Based on Endothelial Cells, Pericytes, and Astrocytes
title_full_unstemmed A New Human Blood–Retinal Barrier Model Based on Endothelial Cells, Pericytes, and Astrocytes
title_short A New Human Blood–Retinal Barrier Model Based on Endothelial Cells, Pericytes, and Astrocytes
title_sort new human blood–retinal barrier model based on endothelial cells, pericytes, and astrocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7084779/
https://www.ncbi.nlm.nih.gov/pubmed/32121029
http://dx.doi.org/10.3390/ijms21051636
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