Dose-dependent benzalkonium chloride toxicity imparts ocular surface epithelial changes with features of dry eye disease.

Animals Benzalkonium Compounds / toxicity Dry Eye Syndromes / chemically induced Mice Mice, Inbred C57BL Ophthalmic Solutions Preservatives, Pharmaceutical / toxicity

Journal

The ocular surface
ISSN: 1937-5913
Titre abrégé: Ocul Surf
Pays: United States
ID NLM: 101156063

Informations de publication

Date de publication:
01 2020
Historique:
received: 01 08 2019
revised: 15 10 2019
accepted: 13 11 2019
pubmed: 20 11 2019
medline: 15 5 2021
entrez: 20 11 2019
Statut: ppublish

Résumé

Inclusion of the preservative benzalkonium chloride (BAC) in ophthalmic solutions is prevalent, despite the noted potential for exacerbating dry eye disease (DED). Whilst studies incorporating BAC have assessed its' effects as a mouse model of DED, the impact on limbal epithelia is under-studied. Our investigation aimed to comprehensively assess the impact of different BAC dosing regimens and their suitability as a mouse model of DED. C57BL/6J mice (n = 72) were administered topical BAC (0.05-0.2%) over 7 days. Fluorescein staining, corneal smoothness index, and immuno-histological analyses were applied to determine architectural and cellular changes on the ocular surface following BAC treatment. The effect of BAC (0.0001-0.01%) on cultivated primary mouse corneo-limbal epithelial cells (CLECs) (n = 6) was examined using morphological and functional assays. Whilst 0.2% BAC induced severe corneal epithelial defects, 0.1% BAC dispensed once daily over 7 days, induced punctate fluorescein staining without detriment to corneal smoothness. Histochemical staining revealed disorganized basal corneal epithelial cells with enlarged cytoplasmic halos. Furthermore, PAS This study describes how exposing C57BL/6 mice to BAC induce some clinicopathological features of DED seen in humans, and therefore provides the foundations to explore the consequences on the ocular surface, particularly on limbal epithelia and its' stem cells.

Identifiants

DOI: 10.1016/j.jtos.2019.11.006 PMID: 31740391
pubmed: 31740391
pii: S1542-0124(19)30285-X
doi: 10.1016/j.jtos.2019.11.006
pii:
doi:

Substances chimiques

Benzalkonium Compounds 0
Ophthalmic Solutions 0
Preservatives, Pharmaceutical 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

158-169

Informations de copyright

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest None of the authors have conflicts of interest to declare.

Auteurs

Richard Zhang (R)

Mechanisms of Disease and Translational Research, School of Medical Sciences, Faculty of Medicine, University of NSW, Sydney, NSW, 2052, Australia.

Mijeong Park (M)

Mechanisms of Disease and Translational Research, School of Medical Sciences, Faculty of Medicine, University of NSW, Sydney, NSW, 2052, Australia.

Alexander Richardson (A)

Mechanisms of Disease and Translational Research, School of Medical Sciences, Faculty of Medicine, University of NSW, Sydney, NSW, 2052, Australia.

Nicodemus Tedla (N)

Mechanisms of Disease and Translational Research, School of Medical Sciences, Faculty of Medicine, University of NSW, Sydney, NSW, 2052, Australia.

Elvis Pandzic (E)

Biomedical Imaging Facility, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, NSW, 2052, Australia.

Cintia S de Paiva (CS)

Department of Ophthalmology, Baylor College of Medicine, Houston, TX, 77030, United States.

Stephanie Watson (S)

Save Sight Institute, Discipline of Ophthalmology, Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia.

Denis Wakefield (D)

Mechanisms of Disease and Translational Research, School of Medical Sciences, Faculty of Medicine, University of NSW, Sydney, NSW, 2052, Australia.

Nick Di Girolamo (N)

Mechanisms of Disease and Translational Research, School of Medical Sciences, Faculty of Medicine, University of NSW, Sydney, NSW, 2052, Australia. Electronic address: n.digirolamo@unsw.edu.au.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Dose-dependent benzalkonium chloride toxicity...
questionsmedicales.fr › Composés chimiques organiques › Composés onium › Composés d'ammonium quaternaire › Composés de benzalkonium › Dose-dependent benzalkonium chloride toxicity...
questionsmedicales.fr › Maladies de l'oeil › Maladies de l'appareil lacrymal › Syndromes de l'oeil sec › Dose-dependent benzalkonium chloride toxicity...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Dose-dependent benzalkonium chloride toxicity...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Dose-dependent benzalkonium chloride toxicity...
questionsmedicales.fr › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Solutions pharmaceutiques › Solutions ophtalmiques › Dose-dependent benzalkonium chloride toxicity...
questionsmedicales.fr › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Excipients pharmaceutiques › Conservateurs pharmaceutiques › Dose-dependent benzalkonium chloride toxicity...