Insights into -Related Ocular Diseases Through Genetics and Animal Studies.

The gene encodes a cytochrome p450 monooxygenase enzyme, and over 150 variants have been associated with a spectrum of eye diseases, including primary congenital glaucoma, anterior segment dysgenesis, juvenile open-angle glaucoma, and primary open-angle glaucoma. Clinical genetics has yielded insights into the functions of the various gene domains; however, animal studies are required to investigate the molecular role of in the eye. While both zebrafish and mice express in the developing eye, embryonic studies have shown disparate species-specific functions. In zebrafish, regulates ocular fissure closure such that overexpression causes a remarkable phenotype consisting of the absence of the posterior eye wall. Adult null zebrafish lack an ocular phenotype but show mild craniofacial abnormalities. In contrast, mice display post-natal mild to severe trabecular meshwork degeneration due to increased oxidative stress damage. Interestingly, the retinal ganglion cells in null mice may be more susceptible to damage secondary to increased intraocular pressure. Future studies, including detailed genotype-phenotype information and animal work elucidating the regulation, substrates, and downstream effects of , will yield important insights for developing molecularly targeted therapies that will aim to prevent vision loss in -related eye diseases.