A New Human Blood-Retinal Barrier Model Based on Endothelial Cells, Pericytes, and Astrocytes.
Int J Mol Sci
; 21(5)2020 Feb 27.
Article
em En
| MEDLINE
| ID: mdl-32121029
ABSTRACT
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-1ß, 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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Retina
/
Barreira Hematorretiniana
/
Astrócitos
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Pericitos
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Células Endoteliais
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Glucose
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Itália