Grant: Operating Grant

For the past 15 years we have used an inherited form of glaucoma, Axenfeld-Rieger Syndrome (ARS), to study the basic mechanisms that cause this blinding condition. Glaucoma is a leading cause of vision loss in Canada, with a prevalence that increases with age. Since the average age of Canadians is increasing, blindness due to glaucoma is of great clinical importance. We have shown that mutation of the forkhead domain C1 (FOXC1) transcription factor causes ARS and glaucoma. We have determined that FOXC1 controls the expression of other genes important in ocular function. Other proteins interact with FOXC1 and in turn regulate FOXC1's function. We thus have first studied FOXC1 to determine how FOXC1 functions, and now plan to use FOXC1 to understand how disruptions in a complex network lead to glaucoma. In this grant proposal we will systematically define the FOXC1 network and then determine its role in glaucoma. We are excited that these proposed experiments might directly lead to improved glaucoma therapies in the short-term.