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

被引：61

作者：

Fresta, Claudia G. ^{[1
]}

Fidilio, Annamaria ^{[2
]}

Caruso, Giuseppe ^{[3
]}

Caraci, Filippo ^{[2
,3
]}

Giblin, Frank J. ^{[4
]}

Marco Leggio, Gian ^{[1
,5
]}

Salomone, Salvatore ^{[1
,5
]}

Drago, Filippo ^{[1
,5
]}

Bucolo, Claudio ^{[1
,4
,5
]}

机构：

[1] Univ Catania, Sch Med, Dept Biomed & Biotechnol Sci, I-95125 Catania, Italy

[2] Univ Catania, Dept Drug Sci, I-95125 Catania, Italy

[3] IRCCS, Oasi Res Inst, I-94018 Troina, Italy

[4] Oakland Univ, Eye Res Inst, Rochester, MI 48309 USA

[5] Univ Catania, Ctr Res Ocular Pharmacol CERFO, I-95125 Catania, Italy

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2020年 / 21卷 / 05期

关键词：

diabetic retinopathy; blood-retinal barrier; astrocytes; oxidative stress; inflammation; NITRIC-OXIDE SYNTHASE; OXIDATIVE STRESS; DIABETIC-RETINOPATHY; NADPH OXIDASE; VE-CADHERIN; MICROCHIP ELECTROPHORESIS; MOLECULAR-BASIS; HIGH GLUCOSE; INFLAMMATION; EXPRESSION;

D O I：

10.3390/ijms21051636

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-1 beta, 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.

引用

页数：17

共 77 条

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