A new human blood–retinal barrier model based on endothelial cells, pericytes, and astrocytes

Claudia G. Fresta, Annamaria Fidilio, Giuseppe Caruso, Filippo Caraci, Frank J. Giblin, Gian Marco Leggio, Salvatore Salomone, Filippo Drago, Claudio Bucolo

Research output: Contribution to journalArticlepeer-review

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-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.

Original languageEnglish
Article number1636
JournalInternational Journal of Molecular Sciences
Volume21
Issue number5
DOIs
Publication statusPublished - Mar 1 2020

Keywords

  • Astrocytes
  • Blood-retinal barrier
  • Diabetic retinopathy
  • Inflammation
  • Oxidative stress

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Fingerprint

Dive into the research topics of 'A new human blood–retinal barrier model based on endothelial cells, pericytes, and astrocytes'. Together they form a unique fingerprint.

Cite this