Abstract

BackgroundDepending 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.ResultsTiO2-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.ConclusionsOverall, our data demonstrate that TiO2-NP can damage endothelial cell function, thereby affecting retinal electrophysiology.

Highlights

  • 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

  • TiO2-NP treatment mildly reduced the cell density of bEnd.3 endothelial cells and Retinal pigment epithelial cell (RPEC) Treatment of bEnd.3 cells with serially diluted TiO2-NPs for 24 h revealed a mild reduction in cell density (% related to control) as determined by an MTT assay

  • The in vitro cytotoxicity of TiO2-NPs at < 1000 ng/mL is limited in bEnd.3 cells and RPECs

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Summary

Introduction

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). Titanium dioxide (TiO2), the naturally occurring oxide of titanium, is abundant in the earth’s crust. It is frequently incorporated in many daily necessities (e.g., toothpaste, food, medicine, and cosmetics) as a white colorant. Sunscreens containing TiO2 macroparticles are often difficult to apply and leave a chalky appearance. These unfavorable disadvantages could be mitigated by shrinking the TiO2 particle size to the nano range. The explosive expansion in the application of TiO2-NPs has led to their safety being highlighted and questioned

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