Funding outcome

Glaucoma is a common disorder caused by elevated intraocular pressure. Childhood cases are frequently associated with visual impairment and on occasion blindness. In childhood, the disorder is primarily caused by impaired flow of aqueous fluid from the eye, which normally drains into a specialized channel, called Schlemm's canal. Recently, this narrow channel was shown to be ciliated, which means it is lined by small structures that beat and move fluid over cells. Our laboratory has discovered that one gene that causes pediatric glaucoma profoundly affects the function of cilia. On the basis of these results, we propose that ciliary dysfunction may more broadly underlie glaucoma. We have undertaken preliminary analysis of related genes, including one that also causes pediatric glaucoma, and observed similar impairment of ciliary function. Based on these findings, we hypothesize that ciliary dysfunction may represent a common mechanism in multiple glaucoma subtypes. This will be evaluated by manipulating the activity of these genes in cultured cells and determining if this affects cilia structure. The experiments will be combined with analysis of signaling pathways important to eye development, which are mediated by cilia. Together these approaches will demonstrate if multiple pediatric glaucoma-causing genes affect cilia and reveal if a common mechanism is shared across pediatric glaucoma. Existence of a common biological target would be important in developing more effective therapies.