Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0081544
Title: Hevin plays a pivotal role in corneal wound healing
Authors: Chaurasia S.S.
Perera P.R. 
Poh R.
Lim R.R.
Wong T.T.
Mehta J.S. 
Keywords: collagen type 1
collagen type 4
hevin
matrix metalloproteinase
scleroprotein
unclassified drug
vasculotropin
animal experiment
animal model
animal tissue
apoptosis
article
chronic inflammation
controlled study
cornea cell
cornea injury
cornea neovascularization
cornea stroma
corneal haze
fibrosis
keratectomy
keratitis
mouse
myofibroblast
nonhuman
ophthalmic excimer laser
protein expression
upregulation
wound healing
Animals
Apoptosis
Calcium-Binding Proteins
Cornea
Corneal Stroma
Extracellular Matrix Proteins
Fibroblasts
Fibrosis
Gene Expression
In Situ Nick-End Labeling
Inflammation
Mice
Mice, Knockout
Neovascularization, Pathologic
Wound Healing
Issue Date: 2013
Publisher: Public Library of Science
Citation: Chaurasia S.S., Perera P.R., Poh R., Lim R.R., Wong T.T., Mehta J.S. (2013). Hevin plays a pivotal role in corneal wound healing. PLoS ONE 8 (11) : e81544. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0081544
Abstract: Background: Hevin is a matricellular protein involved in tissue repair and remodeling via interaction with the surrounding extracellular matrix (ECM) proteins. In this study, we examined the functional role of hevin using a corneal stromal wound healing model achieved by an excimer laser-induced irregular phototherapeutic keratectomy (IrrPTK) in hevin-null (hevin -/-) mice. We also investigated the effects of exogenous supplementation of recombinant human hevin (rhHevin) to rescue the stromal cellular components damaged by the excimer laser. Methodology/Principal Findings: Wild type (WT) and hevin-/- mice were divided into three groups at 4 time points-1, 2, 3 and 4 weeks. Group I served as naïve without any treatment. Group II received epithelial debridement and underwent IrrPTK using excimer laser. Group III received topical application of rhHevin after IrrPTK surgery for 3 days. Eyes were analyzed for corneal haze and matrix remodeling components using slit lamp biomicroscopy, in vivo confocal microscopy, light microscopy (LM), transmission electron microscopy (TEM), immunohistochemistry (IHC) and western blotting (WB). IHC showed upregulation of hevin in IrrPTK-injured WT mice. Hevin-/- mice developed corneal haze as early as 1-2 weeks post IrrPTK-treatment compared to the WT group, which peaked at 3-4 weeks. They also exhibited accumulation of inflammatory cells, fibrotic components of ECM proteins and vascularized corneas as seen by IHC and WB. LM and TEM showed activated keratocytes (myofibroblasts), inflammatory debris and vascular tissues in the stroma. Exogenous application of rhHevin for 3 days reinstated inflammatory index of the corneal stroma similar to WT mice. Conclusions/Significance: Hevin is transiently expressed in the IrrPTK-injured corneas and loss of hevin predisposes them to aberrant wound healing. Hevin -/- mice develop early corneal haze characterized by severe chronic inflammation and stromal fibrosis that can be rescued with exogenous administration of rhHevin. Thus, hevin plays a pivotal role in the corneal wound healing. Copyright: © 2013 Chaurasia et al.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/165965
ISSN: 19326203
DOI: 10.1371/journal.pone.0081544
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