Nervonoylceramide (C24

1Cer), a lipid biomarker for ocular irritants released from the 3D reconstructed human cornea-like epithelium, MCTT HCE™

Miri Lee, Kyung Mi Joo, Seunghye Choi, Su Hyon Lee, Seol Yeong Kim, Young Jin Chun, DalWoong Choi, Kyung Min Lim

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Due to invasive and painful procedures during in vivo rabbit eye irritation test, in vitro alternative methods have been widely investigated. Recently, 3D reconstructed human cornea-like epitheliums (RhCEs) garner a huge attention. RhCEs employ the tissue viability as a primary endpoint to determine ocular irritancy but additional biomarkers may improve its predictive capacity. Here, we explored lipid biomarkers for ocular irritants in MCTT HCE™ RhCE model. Three irritants; sodium lauryl sulfate, benzalkonium chloride and triton X-100 were selected to represent anionic, cationic and non-ionic detergent respectively. After treating MCTT HCE™ with irritants, the alteration of lipids in the treated tissues was examined with Nile Red staining, which revealed the depletion of corneal lipids. We further quantitated the release of ceramides and free fatty acids, major lipid components of cornea, into the medium during the post-treatment incubation, employing a sensitive UPLC-MS/MS method. Among 44 lipid species, nervonoylceramide (C24:1Cer) was found to be released commonly by all three irritants in a concentration-dependent manner. Tests with 10 additional reference substances further supported that C24:1Cer release was significantly correlated with viability. Examination of the genes involved in the biosynthetic pathway for C24:1Cer revealed that stearoylCoA desaturase (SCD) and elongase1 (ELOVL1) were upregulated, suggesting that lipids and related genes may be employed as biomarkers for ocular irritants.

Original languageEnglish
Pages (from-to)94-102
Number of pages9
JournalToxicology in Vitro
Volume47
DOIs
Publication statusPublished - 2018 Mar 1

Fingerprint

Irritants
Biomarkers
Cornea
Epithelium
Lipids
Genes
Tissue
Benzalkonium Compounds
Tissue Survival
Ceramides
Biosynthetic Pathways
Octoxynol
Nonesterified Fatty Acids
Sodium Dodecyl Sulfate
Detergents
HCE
Staining and Labeling
Rabbits

Keywords

  • 3D reconstructed human cornea-like epithelium
  • Eye irritation
  • Lipidomics
  • Nervonoylceramide. C24:1 ceramide

ASJC Scopus subject areas

  • Toxicology

Cite this

Nervonoylceramide (C24 : 1Cer), a lipid biomarker for ocular irritants released from the 3D reconstructed human cornea-like epithelium, MCTT HCE™. / Lee, Miri; Joo, Kyung Mi; Choi, Seunghye; Lee, Su Hyon; Kim, Seol Yeong; Chun, Young Jin; Choi, DalWoong; Lim, Kyung Min.

In: Toxicology in Vitro, Vol. 47, 01.03.2018, p. 94-102.

Research output: Contribution to journalArticle

Lee, Miri ; Joo, Kyung Mi ; Choi, Seunghye ; Lee, Su Hyon ; Kim, Seol Yeong ; Chun, Young Jin ; Choi, DalWoong ; Lim, Kyung Min. / Nervonoylceramide (C24 : 1Cer), a lipid biomarker for ocular irritants released from the 3D reconstructed human cornea-like epithelium, MCTT HCE™. In: Toxicology in Vitro. 2018 ; Vol. 47. pp. 94-102.
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