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Titanium dioxide nanoparticles impair the inner blood-retinal barrier and retinal electrophysiology through rapid ADAM17 activation and claudin-5 degradation


Chan, Y-J and Liao, P-L and Tsai, C-H and Cheng, Y-W and Lin, F-L and Ho, J-D and Chen, C-Y and Li, C-H, Titanium dioxide nanoparticles impair the inner blood-retinal barrier and retinal electrophysiology through rapid ADAM17 activation and claudin-5 degradation, Particle and Fibre Toxicology, 18, (1) pp. 1-16. ISSN 1743-8977 (2021) [Refereed Article]


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Copyright 2021 the Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

DOI: doi:10.1186/s12989-020-00395-7


Background:Depending on their distinct properties, titanium dioxide nanoparticles (TiO2-NPs) are manufactured extensively and widely present in our daily necessities, with growing environmental release and public concerns. In sunscreen formulations, supplementation of TiO2-NPs may reach up to 25% (w/w). Ocular contact with TiO2-NPs may occur accidentally in certain cases, allowing undesirable risks to human vision. This study aimed to understand the barrier integrity of retinal endothelial cells in response to TiO2-NP exposure. bEnd.3 cells and human retinal endothelial cells (HRECs) were exposed to TiO2-NP, followed by examination of their tight junction components and functions.

Results: TiO2-NP treatment apparently induced a broken structure of the junctional plaques, conferring decreased transendothelial electrical resistance, a permeable paracellular cleft, and improved cell migration in vitro. This might involve rapid activation of metalloproteinase, a disintegrin and metalloproteinase 17 (ADAM17), and ADAM17- mediated claudin-5 degradation. For the in vivo study, C57BL/6 mice were administered a single dose of TiO2-NP intravitreally and then subjected to a complete ophthalmology examination. Fluorescein leakage and reduced blood flow at the optical disc indicated a damaged inner blood-retinal barrier induced by TiO2-NPs. Inappreciable change in the thickness of retinal sublayers and alleviated electroretinography amplitude were observed in the TiO2-NP-treated eyes.

Conclusions: Overall, our data demonstrate that TiO2-NP can damage endothelial cell function, thereby affecting retinal electrophysiology.

Item Details

Item Type:Refereed Article
Keywords:titanium dioxide nanoparticles, endothelial cells, claudin-5, ADAM17, blood-retinal barrier
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Diagnosis of human diseases and conditions
UTAS Author:Lin, F-L (Dr Fan-Li Lin)
ID Code:146231
Year Published:2021
Web of Science® Times Cited:6
Deposited By:Menzies Institute for Medical Research
Deposited On:2021-08-25
Last Modified:2021-12-24
Downloads:15 View Download Statistics

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