Yen-Ju Chan1,2, Po-Lin Liao3,4, Chi-Hao Tsai3,4, Yu-Wen Cheng3, Fan-Li Lin5, Jau-Der Ho6, Ching-Yi Chen1,2,3, Ching-Hao Li7,8. 1. Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan. 2. Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei, 110, Taiwan. 3. School of Pharmacy, Taipei Medical University, Taipei, Taiwan. 4. Institute of Food Safety and Health Risk Assessment, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan. 5. Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia. 6. Department of Ophthalmology, Taipei Medical University, Taipei, Taiwan. 7. Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan. bros22@tmu.edu.tw. 8. Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei, 110, Taiwan. bros22@tmu.edu.tw.
Abstract
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.
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.
Authors: Su-Eon Jin; Eun-Ju Kim; Hyunmin Kim; Hyunzu Kim; Woochul Hwang; Seok Won Hong Journal: Mater Sci Eng C Mater Biol Appl Date: 2020-03-13 Impact factor: 7.328
Authors: Krista M Cosert; Soohyun Kim; Iman Jalilian; Maggie Chang; Brooke L Gates; Kent E Pinkerton; Laura S Van Winkle; Vijay Krishna Raghunathan; Brian C Leonard; Sara M Thomasy Journal: Pharmaceutics Date: 2022-05-03 Impact factor: 6.525