Ocular phenotypic consequences of a single copy deletion of the gene ( ) in mice.

PURPOSE

To identify the effects of a single copy deletion of ( ) in the mouse eye, the ocular phenotypic consequences of were determined in detail.

METHODS

Complete ophthalmic examinations, as well as corneal esthesiometry, the phenol red thread test, intraocular pressure, and Fourier-domain optical coherence tomography were performed on and age-matched wild-type (WT) mice between eyelid opening (2 weeks after birth) and adulthood (2 months and 1 year after birth). Following euthanasia, enucleated eyes were characterized histologically.

RESULTS

Microphthalmia with small palpebral fissures, corneal fibrosis, and reduced corneal sensation were common findings in the mice. Generalized corneal fibrosis precluded clinical examination of the posterior structures. Histologically, thinning and keratinization of the corneal epithelium were observed in the mice in comparison with the WT mice. Distorted collagen fiber arrangement and hypercellularity of keratocytes were observed in the stroma. Descemet's membrane was extremely thin and lacked an endothelial layer in the mice. The iris was adherent to the posterior cornea along most of its surface creating a distorted contour. Most of the eyes were microphakic with swollen fibers and bladder cells. The retinas of the mice were normal at 2 weeks and 2 months of age, but the presence of retinal abnormalities, including retinoschisis and detachment, was markedly increased in the mice at 1 year of age.

CONCLUSIONS

The results show that the heterozygous deletion of the gene in mice leads to complex ocular abnormalities, including microphthalmia, corneal fibrosis, anterior segment dysgenesis, and cataract.