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 language | English |
|---|---|
| Pages (from-to) | 3104-3114 |
| Number of pages | 11 |
| Journal | Investigative Ophthalmology and Visual Science |
| Volume | 59 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2018 Jun 1 |
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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 journal › Article
}
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 -