Effects of topical mucolytic agents on the tears and ocular surface: a plausible animal model of mucin-deficient dry eye

Xiangzhe Li, Boram Kang, In Ho Woo, Youngsub Eom, Hyung Keun Lee, Hyo Myung Kim, Jong-Suk Song

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

PURPOSE. A topical mucolytic agent, N-acetylcysteine (NAC), has been used to create an animal model without the intestinal mucus layer. In this study, we investigated the effects of topical NAC on the tears and ocular surface. METHODS. NAC-treated models were established by topically administering 10% NAC four times daily for 5 days in male Sprague-Dawley rats. Clinical parameters and the expression of mucin proteins and genes were evaluated. Alterations in the conjunctival epithelium and goblet cells were observed. RESULTS. The NAC group showed significant decreases in tear secretion, corneal wetting ability, tear MUC5AC concentration, and conjunctival goblet cell numbers as compared with the control group (all P <0.01). In addition, significant increases in corneal fluorescein score and rose bengal scores were observed in the NAC group versus in the control group (P <0.05 and P <0.01, respectively). Hematoxylin and eosin (H&E) staining and scanning electron microscopy clearly showed damage in the epithelial cell layer and microvilli of the NAC group. Although there was no significant difference in MUC16 gene expression, the MUC16 concentration of the tear film and ocular surface tissue was significantly increased in the NAC group versus in the control group (P <0.01 and P <0.05, respectively). Five-day treatment with 3% diquafosol had minimal therapeutic effect in NAC-treated rat eyes. CONCLUSIONS. Topical administration of 10% NAC induced ocular surface damage and tear film instability by prompting MUC16 disruption and release from the ocular surface. This animal model could be used to study dry eye disease, especially the mucin-deficiency subtype.

Original languageEnglish
Pages (from-to)3104-3114
Number of pages11
JournalInvestigative Ophthalmology and Visual Science
Volume59
Issue number7
DOIs
Publication statusPublished - 2018 Jun 1

Fingerprint

Expectorants
Acetylcysteine
Mucins
Tears
Animal Models
Goblet Cells
Control Groups
Rose Bengal
Topical Administration
Eye Diseases
Therapeutic Uses
Mucus
Hematoxylin
Eosine Yellowish-(YS)
Microvilli
Fluorescein
Electron Scanning Microscopy
Sprague Dawley Rats
Epithelium
Cell Count

Keywords

  • Dry eye
  • Goblet cell
  • MUC1
  • MUC16
  • MUC5AC
  • N-acetylcysteine
  • Ocular surface damage

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Effects of topical mucolytic agents on the tears and ocular surface : a plausible animal model of mucin-deficient dry eye. / Li, Xiangzhe; Kang, Boram; Woo, In Ho; Eom, Youngsub; Lee, Hyung Keun; Kim, Hyo Myung; Song, Jong-Suk.

In: Investigative Ophthalmology and Visual Science, Vol. 59, No. 7, 01.06.2018, p. 3104-3114.

Research output: Contribution to journalArticle

@article{b0f12b142b9145438b503290c4d1e1f1,
title = "Effects of topical mucolytic agents on the tears and ocular surface: a plausible animal model of mucin-deficient dry eye",
abstract = "PURPOSE. A topical mucolytic agent, N-acetylcysteine (NAC), has been used to create an animal model without the intestinal mucus layer. In this study, we investigated the effects of topical NAC on the tears and ocular surface. METHODS. NAC-treated models were established by topically administering 10{\%} NAC four times daily for 5 days in male Sprague-Dawley rats. Clinical parameters and the expression of mucin proteins and genes were evaluated. Alterations in the conjunctival epithelium and goblet cells were observed. RESULTS. The NAC group showed significant decreases in tear secretion, corneal wetting ability, tear MUC5AC concentration, and conjunctival goblet cell numbers as compared with the control group (all P <0.01). In addition, significant increases in corneal fluorescein score and rose bengal scores were observed in the NAC group versus in the control group (P <0.05 and P <0.01, respectively). Hematoxylin and eosin (H&E) staining and scanning electron microscopy clearly showed damage in the epithelial cell layer and microvilli of the NAC group. Although there was no significant difference in MUC16 gene expression, the MUC16 concentration of the tear film and ocular surface tissue was significantly increased in the NAC group versus in the control group (P <0.01 and P <0.05, respectively). Five-day treatment with 3{\%} diquafosol had minimal therapeutic effect in NAC-treated rat eyes. CONCLUSIONS. Topical administration of 10{\%} NAC induced ocular surface damage and tear film instability by prompting MUC16 disruption and release from the ocular surface. This animal model could be used to study dry eye disease, especially the mucin-deficiency subtype.",
keywords = "Dry eye, Goblet cell, MUC1, MUC16, MUC5AC, N-acetylcysteine, Ocular surface damage",
author = "Xiangzhe Li and Boram Kang and Woo, {In Ho} and Youngsub Eom and Lee, {Hyung Keun} and Kim, {Hyo Myung} and Jong-Suk Song",
year = "2018",
month = "6",
day = "1",
doi = "10.1167/iovs.18-23860",
language = "English",
volume = "59",
pages = "3104--3114",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "7",

}

TY - JOUR

T1 - Effects of topical mucolytic agents on the tears and ocular surface

T2 - a plausible animal model of mucin-deficient dry eye

AU - Li, Xiangzhe

AU - Kang, Boram

AU - Woo, In Ho

AU - Eom, Youngsub

AU - Lee, Hyung Keun

AU - Kim, Hyo Myung

AU - Song, Jong-Suk

PY - 2018/6/1

Y1 - 2018/6/1

N2 - PURPOSE. A topical mucolytic agent, N-acetylcysteine (NAC), has been used to create an animal model without the intestinal mucus layer. In this study, we investigated the effects of topical NAC on the tears and ocular surface. METHODS. NAC-treated models were established by topically administering 10% NAC four times daily for 5 days in male Sprague-Dawley rats. Clinical parameters and the expression of mucin proteins and genes were evaluated. Alterations in the conjunctival epithelium and goblet cells were observed. RESULTS. The NAC group showed significant decreases in tear secretion, corneal wetting ability, tear MUC5AC concentration, and conjunctival goblet cell numbers as compared with the control group (all P <0.01). In addition, significant increases in corneal fluorescein score and rose bengal scores were observed in the NAC group versus in the control group (P <0.05 and P <0.01, respectively). Hematoxylin and eosin (H&E) staining and scanning electron microscopy clearly showed damage in the epithelial cell layer and microvilli of the NAC group. Although there was no significant difference in MUC16 gene expression, the MUC16 concentration of the tear film and ocular surface tissue was significantly increased in the NAC group versus in the control group (P <0.01 and P <0.05, respectively). Five-day treatment with 3% diquafosol had minimal therapeutic effect in NAC-treated rat eyes. CONCLUSIONS. Topical administration of 10% NAC induced ocular surface damage and tear film instability by prompting MUC16 disruption and release from the ocular surface. This animal model could be used to study dry eye disease, especially the mucin-deficiency subtype.

AB - PURPOSE. A topical mucolytic agent, N-acetylcysteine (NAC), has been used to create an animal model without the intestinal mucus layer. In this study, we investigated the effects of topical NAC on the tears and ocular surface. METHODS. NAC-treated models were established by topically administering 10% NAC four times daily for 5 days in male Sprague-Dawley rats. Clinical parameters and the expression of mucin proteins and genes were evaluated. Alterations in the conjunctival epithelium and goblet cells were observed. RESULTS. The NAC group showed significant decreases in tear secretion, corneal wetting ability, tear MUC5AC concentration, and conjunctival goblet cell numbers as compared with the control group (all P <0.01). In addition, significant increases in corneal fluorescein score and rose bengal scores were observed in the NAC group versus in the control group (P <0.05 and P <0.01, respectively). Hematoxylin and eosin (H&E) staining and scanning electron microscopy clearly showed damage in the epithelial cell layer and microvilli of the NAC group. Although there was no significant difference in MUC16 gene expression, the MUC16 concentration of the tear film and ocular surface tissue was significantly increased in the NAC group versus in the control group (P <0.01 and P <0.05, respectively). Five-day treatment with 3% diquafosol had minimal therapeutic effect in NAC-treated rat eyes. CONCLUSIONS. Topical administration of 10% NAC induced ocular surface damage and tear film instability by prompting MUC16 disruption and release from the ocular surface. This animal model could be used to study dry eye disease, especially the mucin-deficiency subtype.

KW - Dry eye

KW - Goblet cell

KW - MUC1

KW - MUC16

KW - MUC5AC

KW - N-acetylcysteine

KW - Ocular surface damage

UR - http://www.scopus.com/inward/record.url?scp=85049072184&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049072184&partnerID=8YFLogxK

U2 - 10.1167/iovs.18-23860

DO - 10.1167/iovs.18-23860

M3 - Article

C2 - 30025127

AN - SCOPUS:85049072184

VL - 59

SP - 3104

EP - 3114

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 7

ER -