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Quantitative assessment of ultrastructure and light scatter in mouse corneal debridement wounds

Boote, Craig, Du, Yiqin, Morgan, Sian Rebecca, Harris, Jonathan, Kamma-Lorger, Christina S., Hayes, Sally, Lathrop, Kira L., Roh, Danny S., Burrow, Michael K., Hiller, Jennifer, Terrill, Nicholas J., Funderburgh, James L. and Meek, Keith Michael Andrew 2012. Quantitative assessment of ultrastructure and light scatter in mouse corneal debridement wounds. Investigative Ophthalmology and Visual Science 53 (6) , pp. 2786-2795. 10.1167/iovs.11-9305

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Abstract

Purpose. The mouse has become an important wound healing model with which to study corneal fibrosis, a frequent complication of refractive surgery. The aim of the current study was to quantify changes in stromal ultrastructure and light scatter that characterize fibrosis in mouse corneal debridement wounds. Methods. Epithelial debridement wounds, with and without removal of basement membrane, were produced in C57BL/6 mice. Corneal opacity was measured using optical coherence tomography, and collagen diameter and matrix order were quantified by x-ray scattering. Electron microscopy was used to visualize proteoglycans. Quantitative PCR (Q-PCR) measured mRNA transcript levels for several quiescent and fibrotic markers. Results. Epithelial debridement without basement membrane disruption produced a significant increase in matrix disorder at 8 weeks, but minimal corneal opacity. In contrast, basement membrane penetration led to increases in light scatter, matrix disorder, and collagen diameter, accompanied by the appearance of abnormally large proteoglycans in the subepithelial stroma. This group also demonstrated upregulation of several quiescent and fibrotic markers 2 to 4 weeks after wounding. Conclusions. Fibrotic corneal wound healing in mice involves extensive changes to collagen and proteoglycan ultrastructure, consistent with deposition of opaque scar tissue. Epithelial basement membrane penetration is a deciding factor determining the degree of ultrastructural changes and resulting opacity.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Optometry and Vision Sciences
Subjects: R Medicine > RE Ophthalmology
Additional Information: Confirmation received by publisher on 21 February 2014 that publisher's pdf can be self-archived 6 months after publication.
Publisher: Association for Research in Vision and Ophthalmology
ISSN: 0146-0404
Funders: MRC
Date of First Compliant Deposit: 30 March 2016
Last Modified: 04 Jun 2017 04:04
URI: http://orca.cf.ac.uk/id/eprint/32013

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