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

Autor: Ching Yi Chen, Jau Der Ho, Ching Hao Li, Fan Li Lin, Po Lin Liao, Yu Wen Cheng, Chi Hao Tsai, Yen Ju Chan
Rok vydání: 2021
Předmět:
Blood-retinal barrier
Endothelial cells
Health
Toxicology and Mutagenesis
lcsh:Industrial hygiene. Industrial welfare
Blood–retinal barrier
Metal Nanoparticles
02 engineering and technology
Toxicology
Mice
03 medical and health sciences
chemistry.chemical_compound
lcsh:RA1190-1270
medicine
Animals
Claudin-5
Claudin
lcsh:Toxicology. Poisons
030304 developmental biology
Titanium
ADAM17
0303 health sciences
medicine.diagnostic_test
Tight junction
Research
technology
industry
and agriculture
Titanium dioxide nanoparticles
Retinal
Cell migration
General Medicine
021001 nanoscience & nanotechnology
Electrophysiology
Mice
Inbred C57BL
Endothelial stem cell
medicine.anatomical_structure
chemistry
Paracellular transport
Biophysics
Nanoparticles
0210 nano-technology
lcsh:HD7260-7780.8
Electroretinography
Zdroj: Particle and Fibre Toxicology
Particle and Fibre Toxicology, Vol 18, Iss 1, Pp 1-16 (2021)
ISSN: 1743-8977
Popis: 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.
Databáze: OpenAIRE
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