Effect of Nitric Oxide on Human Corneal Epithelial Cell Viability and Corneal Wound Healing

Abstract Although the wound healing effects of nitric oxide (NO) are known, the mechanism by which NO modulates corneal wound healing remains unclear. In this study, we investigated the effect of exogenous NO donor (NaNO2) on corneal wound healing. We found that NaNO2 (0.1 μM to 100 μM) increased hu...

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Main Authors: Joo-Hee Park, Ja-Yeon Kim, Dong Ju Kim, Martha Kim, Minwook Chang, Roy S. Chuck, Choul Yong Park
Format: Article
Language:English
Published: Nature Publishing Group 2017-08-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-017-08576-9
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spelling doaj-d76c32beac364cada601b8d529653f642020-12-08T02:40:30ZengNature Publishing GroupScientific Reports2045-23222017-08-017111010.1038/s41598-017-08576-9Effect of Nitric Oxide on Human Corneal Epithelial Cell Viability and Corneal Wound HealingJoo-Hee Park0Ja-Yeon Kim1Dong Ju Kim2Martha Kim3Minwook Chang4Roy S. Chuck5Choul Yong Park6Department of Ophthalmology, Dongguk University, Ilsan HospitalDepartment of Ophthalmology, Dongguk University, Ilsan HospitalDepartment of Ophthalmology, Dongguk University, Ilsan HospitalDepartment of Ophthalmology, Dongguk University, Ilsan HospitalDepartment of Ophthalmology, Dongguk University, Ilsan HospitalDepartment of Ophthalmology and Visual Sciences, Montefiore Medical Center, Albert Einstein College of MedicineDepartment of Ophthalmology, Dongguk University, Ilsan HospitalAbstract Although the wound healing effects of nitric oxide (NO) are known, the mechanism by which NO modulates corneal wound healing remains unclear. In this study, we investigated the effect of exogenous NO donor (NaNO2) on corneal wound healing. We found that NaNO2 (0.1 μM to 100 μM) increased human corneal epithelial cell (HCEC) viability and migration. It also modulated the phosphorylation of mitogen-activated protein kinases (MAPKs) in a time- dependent manner in those HCECs. Further, p38 MAPK phosphorylation increased at 6 h and normalized at 24 h, while the phosphorylation of extracellular signal regulated kinase (ERK) was increased both at 6 h and 24 h. Topical treatment with NaNO2 (10 μM) enhanced corneal epithelial healing and decreased corneal opacity in murine corneal alkali burn model by modulating inflammatory cytokines. Our findings suggest that NO increased HCEC proliferation and migration via time-dependent MAPK activation and eventually enhanced corneal recovery from the alkali burn.https://doi.org/10.1038/s41598-017-08576-9
collection DOAJ
language English
format Article
sources DOAJ
author Joo-Hee Park
Ja-Yeon Kim
Dong Ju Kim
Martha Kim
Minwook Chang
Roy S. Chuck
Choul Yong Park
spellingShingle Joo-Hee Park
Ja-Yeon Kim
Dong Ju Kim
Martha Kim
Minwook Chang
Roy S. Chuck
Choul Yong Park
Effect of Nitric Oxide on Human Corneal Epithelial Cell Viability and Corneal Wound Healing
Scientific Reports
author_facet Joo-Hee Park
Ja-Yeon Kim
Dong Ju Kim
Martha Kim
Minwook Chang
Roy S. Chuck
Choul Yong Park
author_sort Joo-Hee Park
title Effect of Nitric Oxide on Human Corneal Epithelial Cell Viability and Corneal Wound Healing
title_short Effect of Nitric Oxide on Human Corneal Epithelial Cell Viability and Corneal Wound Healing
title_full Effect of Nitric Oxide on Human Corneal Epithelial Cell Viability and Corneal Wound Healing
title_fullStr Effect of Nitric Oxide on Human Corneal Epithelial Cell Viability and Corneal Wound Healing
title_full_unstemmed Effect of Nitric Oxide on Human Corneal Epithelial Cell Viability and Corneal Wound Healing
title_sort effect of nitric oxide on human corneal epithelial cell viability and corneal wound healing
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2017-08-01
description Abstract Although the wound healing effects of nitric oxide (NO) are known, the mechanism by which NO modulates corneal wound healing remains unclear. In this study, we investigated the effect of exogenous NO donor (NaNO2) on corneal wound healing. We found that NaNO2 (0.1 μM to 100 μM) increased human corneal epithelial cell (HCEC) viability and migration. It also modulated the phosphorylation of mitogen-activated protein kinases (MAPKs) in a time- dependent manner in those HCECs. Further, p38 MAPK phosphorylation increased at 6 h and normalized at 24 h, while the phosphorylation of extracellular signal regulated kinase (ERK) was increased both at 6 h and 24 h. Topical treatment with NaNO2 (10 μM) enhanced corneal epithelial healing and decreased corneal opacity in murine corneal alkali burn model by modulating inflammatory cytokines. Our findings suggest that NO increased HCEC proliferation and migration via time-dependent MAPK activation and eventually enhanced corneal recovery from the alkali burn.
url https://doi.org/10.1038/s41598-017-08576-9
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