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S. Chen, W. W. Kao, D. E. Birk; Dysfunctional Regulation of Extracellular Matrix Assembly in a Mouse Model of Human Congenital Stromal Corneal Dystrophy. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3832.
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© ARVO (1962-2015); The Authors (2016-present)
Congenital stromal corneal dystrophy is associated with a mutant decorin gene, resulting in a truncated protein core lacking the C-terminal 33 amino acids. A mouse model of the human disease was developed to investigate the role(s) of decorin in matrix assembly in the normal development and pathobiology of the corneal stroma.
Using a Cre-on approach, a transgenic mouse model was developed. Mutant decorin expression comparable to that in human congenital corneal stromal dystrophy was targeted to the cornea stroma. The mouse model was analyzed using immunochemical, morphological and molecular/biochemical approaches.
The transgenic cornea-specific decorin mutant mice developed cloudy corneas. Ultrastructural analysis demonstrated a comparable endothelium and Decemet’s membrane in transgenic and control mice. However, a disorganized orthogonal lamellar structure was observed in the corneal stroma of the transgenic mice. This phenotype was most obvious in the posterior cornea. Lamellae with relatively normal collagen fibrils were separated by layers of abnormal filaments embedded in an abnormal lucent ground substance. Within these abnormal regions there was increased inter-filament/fibril spacing/organization. The abnormal regions were adjacent to keratocytes. Immunohistochemical analysis revealed reduced reactivity of both class II SLRPs, lumican and keratocan, in the posterior cornea in transgenic decorin mutant mice compared to wild type mice, suggesting an interaction between decorin and other SLRPs in the dysfunctional regulation.
The phenotype in our mouse model was comparable to that in human disease of congenital stromal corneal dystrophy. Interaction of class II SLRRs may be involved in the dysfunctional regulation of corneal stroma matrix assembly caused by mutant decorin.
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