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Ezrin as a complementary marker in ocular toxicity assessment using a three-dimensional reconstructed human corneal-like epithelium model, EpiOcular™.

Abstract：

INTRODUCTION:A variety of in vitro tests to replace the Draize test have been developed; however, there is no available method for assessing the full spectrum of Globally Harmonized System (GHS) categories. Human cornea-like three-dimensional (3D) reconstructed tissue models are the most promising in vitro systems. The objective of this study was to evaluate the ocular toxicity of 11 test substances using the EpiOcular™ model after performing proficiency tests. We further evaluated the effectiveness of ezrin staining as a complementary marker in histological analysis to overcome the limitation of eye irritation tests using 3D reconstructed human corneal epithelium models. METHODS:The assessment of ocular toxicity was performed by the suggested OECD TG 492 procedure. After treatment with proficiency test chemicals and 10 test substances, EpiOcular™ tissue models were stained with hematoxylin and eosin and ezrin, and the histological changes were observed by immunofluorescence microscopy. RESULTS:The ocular toxicity assessment of 10 test chemicals using the EpiOcular™ eye irritation test were in accordance with the UN GHS classification of test chemicals. Histological analysis of ezrin staining showed that the cell membranes of models treated with 10 out of 11 non-irritant chemicals were maintained, whereas those of models treated with 14 eye irritant substances resulted in the apparent translocation of ezrins from the cell membrane to the cytoplasm or nucleus by destruction of cell membrane. DISCUSSION:Ezrin may be used as a complementary marker to more accurately assess ocular toxicity using 3D reconstructed human cornea-like epithelium models.

journal_name

J Pharmacol Toxicol Methods

journal_title

Journal of pharmacological and toxicological methods

authors

Ko KY,Hong M,Kim TS,Nam KT,Lee G,Yi JS,Ahn IY,Kim JH,Lee JK

doi

10.1016/j.vascn.2018.02.007

subject

Has Abstract

pub_date

2018-01-01 00:00:00

pages

24-33

eissn

1056-8719

issn

1873-488X

pii

S1056-8719(17)30190-9

journal_volume

pub_type

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Ezrin as a complementary marker in ocular toxicity assessment using a three-dimensional reconstructed human corneal-like epithelium model, EpiOcular™.