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

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journal contribution
posted on 2023-05-21, 01:53 authored by Chan, Y-J, Liao, P-L, Tsai, C-H, Cheng, Y-W, Fan-Li Lin, Ho, J-D, Chen, C-Y, Li, C-H

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.


Publication title

Particle and Fibre Toxicology








Menzies Institute for Medical Research


BioMed Central Ltd.

Place of publication

United Kingdom

Rights statement

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

Repository Status

  • Open

Socio-economic Objectives

Diagnosis of human diseases and conditions

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