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Hevin plays a pivotal role in corneal wound healing


Chaurasia, SS and Perera, PR and Poh, R and Lim, RR and Wong, TT and Mehta, JS, Hevin plays a pivotal role in corneal wound healing, PLoS One, 8, (11) Article e81544. ISSN 1932-6203 (2013) [Refereed Article]


Copyright Statement

Copyright 2013 Chaurasia et al. Licensed under Creative Commons Attribution 3.0 Unported (CC BY 3.0)

DOI: doi:10.1371/journal.pone.0081544


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 na´ve 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.

Item Details

Item Type:Refereed Article
Keywords:corneal wound wealing
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Perera, PR (Mrs Agampodi Perera)
ID Code:127177
Year Published:2013
Web of Science® Times Cited:10
Deposited By:Health Sciences
Deposited On:2018-07-16
Last Modified:2018-08-09
Downloads:73 View Download Statistics

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