Corneal abnormalities in Pax6+/- small eye mice mimic human aniridia-related keratopathy.

PURPOSE: To investigate corneal abnormalities in heterozygous Pax6(+/Sey-Neu) (Pax6(+/-), small eye) mice and compare them with aniridia-related keratopathy in PAX6(+/-) patients.
METHODS: Fetal and postnatal corneal histopathology, adult corneal thickness, and the distribution of K12-immunostained cells were compared in wild-type and Pax6(+/-) mice.
RESULTS: Prenatally, the corneal epithelium was thinner in Pax6(+/-) fetuses than wild-type littermates, but the stroma appeared irregular, hypercellular, and thickened. The anterior chamber angle was obliterated, and the iris was hypoplastic from early developmental stages. The adult Pax6(+/-) corneal epithelium was thinner, had fewer layers, and included goblet cells, indicating repopulation from conjunctival epithelium. The ocular surface was often roughened, with epithelial vacuolation and lens tissue within the stroma. The corneal stroma was thicker centrally, with an irregular lamellar alignment. Many adult Pax6(+/-) corneas were vascularized or contained cellular infiltrates, but some remained clear. Corneal degeneration was age-related: Older Pax6(+/-) mice had prominent subepithelial pannus and more goblet cells in the peripheral corneal epithelium. Cytokeratin 12 stained very weakly in the peripheral and superficial corneal epithelium in 12-month-old Pax6(+/-) mice.
CONCLUSIONS: Corneal abnormalities in Pax6(+/-) mice are similar to those in aniridia-related keratopathy in PAX6(+/-) patients. This extends the relevance of this mouse model of human aniridia to include corneal abnormalities. Incursion of goblet cells suggests impaired function of Pax6(+/-) limbal stem cells, abnormal expression of cytokeratin 12 may result in greater epithelial fragility, and corneal opacities in older mice may reflect poor wound-healing responses to accumulated environmental insults.