Extracellular Matrix Deposition and Remodeling after Corneal Alkali Burn in Mice.

Kazadi N Mutoji,Clare Hughes,Mingxia Sun,Isabel Y Moreno,Tarsis F Gesteira,Vivien J Coulson-Thomas,Garrett Elliott

doi:10.3390/ijms22115708

Abstract

Corneal transparency relies on the precise arrangement and orientation of collagen fibrils, made of mostly Type I and V collagen fibrils and proteoglycans (PGs). PGs are essential for correct collagen fibrillogenesis and maintaining corneal homeostasis. We investigated the spatial and temporal distribution of glycosaminoglycans (GAGs) and PGs after a chemical injury. The chemical composition of chondroitin sulfate (CS)/dermatan sulfate (DS) and heparan sulfate (HS) were characterized in mouse corneas 5 and 14 days after alkali burn (AB), and compared to uninjured corneas. The expression profile and corneal distribution of CS/DSPGs and keratan sulfate (KS) PGs were also analyzed. We found a significant overall increase in CS after AB, with an increase in sulfated forms of CS and a decrease in lesser sulfated forms of CS. Expression of the CSPGs biglycan and versican was increased after AB, while decorin expression was decreased. We also found an increase in KS expression 14 days after AB, with an increase in lumican and mimecan expression, and a decrease in keratocan expression. No significant changes in HS composition were noted after AB. Taken together, our study reveals significant changes in the composition of the extracellular matrix following a corneal chemical injury.

Highlights

The cornea is a transparent tissue that forms the outermost part of the eye and is responsible for the initial refraction of light from the external environment into the eye, and onto the retina, resulting in the manifestation of an image [1,2,3]
Highly sulfated chondroitin sulfate (CS) could potentially play a role in the provisional matrix during wound healing, and, be part of the corneal scarring process
We used the well-established alkali burn (AB) mouse model to assess the change in GAG composition during corneal wound healing 5 and 14 days after a chemical injury

Summary

Introduction

The cornea is a transparent tissue that forms the outermost part of the eye and is responsible for the initial refraction of light from the external environment into the eye, and onto the retina, resulting in the manifestation of an image [1,2,3]. The stroma is composed of a highly organized network of largely Type I and V collagen fibrils with an extracellular matrix (ECM) consisting of four main structural components, water, salts, glycoproteins, and proteoglycans (PGs) [3,13]. The Chakravarti group was able to demonstrate that lumican null mice present corneal opacity as a result of increased fibril diameter, altered fibril structures and increased interfibrillary spacing, all due to a reduction in total KSPG levels [29,30]. A similar increase in collagen fibril diameter was observed in a different study using mimecan null mice [21] Since these early findings many other studies have further shown that KSPGs and CS/DSPGs play a key role in establishing and maintaining corneal transparency by maintaining structural integrity of collagen fibrils [18,31,32]

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Results

Conclusion