Genes Involved in Anterior Segment Dysgenesis and Glaucoma

Glaucoma is one of the leading causes of visual disability in the United States (more than 2.7 million cases) and throughout the world (more than 60 million cases). There are certain developmental ocular disorders in humans that can lead to glaucoma. The goals of this proposal are to determine the genes involved in a group of developmental disorders known as anterior segment dysgenesis (ASD), which can lead to glaucoma, as well as create animal models of glaucoma to further understand the pathophysiology of the disease and how we may cure it.

Anterior segment dysgenesis (ASD) is a developmental anomaly of the eye that is associated with an increased risk of glaucoma. ASD can involve multiple tissues, including the cornea, iris, lens, ciliary body and ocular drainage structures (eg, the trabecular meshwork, or TM, and Schlemm’s canal). In fact, it’s estimated that glaucoma will arise in 50 percent of humans with ASD due to disruption in aqueous humour drainage that leads to an elevation in intraocular pressure (IOP).

Our laboratory has developed a new mouse model of ASD in which an important gene (AP-2beta) has been deleted in the anterior segment of the eye. Analysis of this exciting new model will include measurement of IOP, assessment of the timing and degree of retinal ganglion cell loss, as well as assessment of subsequent optic nerve axon degeneration. Additional genetic models of ASD and glaucoma will be also be generated by our lab by deleting the AP-2beta gene in specific ocular tissues. The findings from these studies are expected to add to the understanding of the genetic cascade controlling anterior segment development, and to the pathophysiology of closed angle glaucoma and optic neuropathy. Our models may also be used for testing promising therapeutic agents for glaucoma.