Corneal epithelial surface disease
Corneal epithelial surface disease is an irregular thickening of the corneal surface that interferes with vision, leads to excessive scarring of corneal wounds, and promotes the development of corneal vascularization. It may be caused by keratitis sicca, xerophthalmia, chemical and thermal burns, ocular cicatricial pemphigoid, Stevens-Johnson syndrome, and numerous skin diseases. Treatment is difficult, but better ones may be found by studying the disease in mouse models.
JAX® Mice Models
| C57BL/6JSmn-Dstncorn1-2J/J |
The corn1 mutant is the first animal model of genetically determined spontaneous corneal epithelial surface disease and neovascularization. Dstncorn1 homozygotes have abnormally proliferative basal corneal epithelial cells, which can be seen by the time they are a week old. Neovascularization can be seen by the time they are two weeks old (when their eyes open), and it progresses during the first two months of their lives. It is not found in mice homozygous for the Dstncorn-2J allele (which is a point mutation leading to a change in a single amino acid residue). In both mutants the corneal epithelial cells show increased levels and an altered organizational pattern of filamentous actin. The areas of thickened cortical epithelia yield a roughened, opaque corneal surface. Expression of keratin 14 and involucrin in four-week old Dstncorn1 homozygotes extends into the suprabasal layer in the areas of hyperplastic corneal epithelia. The mutants also express increased levels of cofilin 1, keratocan, and lumican (which is abnormally expressed in epithelial cells).
| A.BY H2bc H2-T18f/SnJ-Dstncorn1/J |
Dstncorn1-2J homozygotes have corneas with thickened epithelia and enlarged surface epithelial cells with degenerating nuclei. They lack the neovascularization of and have a more mild corneal epithelial phenotype than Dstncorn1 homozygotes. Preliminary assessment indicates that this variation in phenotype results from the distinct mutations in Dstn, not from differences in genetic background. The corneal epithelial cells of both mutants show increased levels and altered organizational patterns of filamentous actin. The alteration to filamentous actin In the Dstncorn1 mutants leads to accelerated proliferation of basal corneal epithelial cells. (Smith et al. 1996; Wang et al. 2001;
Ikeda et al. 2003.)
References
Ikeda S, Cunningham LA, Boggess D, Hobson CD, Sundberg JP, Naggert JK, Smith RS, Nishina PM 2003. Aberrant actin cytoskeleton leads to accelerated proliferation of corneal epithelial cells in mice deficient for destrin (actin depolymerizing factor). Hum Mol Genet 12:1029-37.
Smith RS, Hawes NL, Kuhlmann SD, Heckenlively JR, Chang B, Roderick TH, Sundberg JP. 1996. Corn1: a mouse model for corneal surface disease and neovascularization. Invest Ophthalmol Vis Sci 37:397-404.
Wang I, Kao CW, Liu C, Saika S, Nishina PM, Sundberg JP, Smith RS, Kao WW. 2001. Characterization of Corn1 mice: Alteration of epithelial and stromal cell gene expression. Mol Vis 7:20-6.
