The C‐terminus of Decorin Regulates Class II Small Leucine Rich Proteoglycans (SLRPs) in Corneal Stromal Matrix Assembly

Abstract

The purpose of this work is to study the regulatory role of the decorin in corneal stromal matrix assembly. In human congenital stromal corneal dystrophy mutant decorin is expressed with a truncated C‐terminus. A transgenic mouse model of the disease was created in a decorin wild type background. Both wild type and mutant decorin were expressed in mutant mice. Corneal opacities developed throughout the stroma in mutant mice, but were more severe in posterior stroma. The orthogonal lamellar structure was disrupted, with relatively normal lamellae separated by abnormal zones. In these abnormal zones, collagen fibrils were heterogeneous in diameter with increased and irregular inter‐fibril spacing. The aberrant zone was more obvious near keratocyte suggested an area differential dysfunctional matrix assembly. Expression of all class II stromal SLRPs was altered in the mutant mouse. Both lumican and keratocan were down‐regulated, and fibromodulin was up‐regulated. The C‐terminus of decorin is implicated in maintenance of protein core conformation and ligand binding. The data suggest that loss of the C‐terminus altered decorin binding directly or indirectly through other extracellular matrix components to keratocytes, changing the interactions between decorin and other SLRPs. These interactions are important for the rigid control of fibrillogenesis and fibril organization in cornea stromal matrix assembly.Grant Funding Source: NIH grants EY05129, AR 44745 (DEB), 2010 postdoctoral fellowship from American Association of Anatomists (SC), 2010 postdoctoral fellowship from Fight for Sight (SC).