Identifying Glaucoma-Promoting Genes Using Zebrafish

The main goal of this study is to identify genes that cause ganglion cell degeneration when intraocular pressure (IOP) is elevated, a key feature of many forms of glaucoma. Using zebrafish that show elevated IOP without associated ganglion cell degeneration, we will screen for ‘interacting’ mutations that lead to injury response pathways in retinal ganglion cells and eventually cause blinding degeneration.

Glaucoma is a leading cause of blindness worldwide and yet our understanding of the genetic basis of this neurodegenerative disease remains largely unknown. One reason for this is that glaucoma is really a collection of diseases and each form is thought to be caused by mutations in multiple genes. Zebrafish are ideal for these studies because they share similar ocular anatomy, physiology and genetics as humans. In addition, zebrafish can be raised in very large numbers at modest cost, facilitating complex forward genetic endeavors. Once the key genes for glaucoma are identified, genetic tests can be developed and ultimately, research for targeted therapies can begin.