AVN Members : Dr. Michael Walter
The Walter Ocular Genetics laboratory at the University of Alberta concentrates upon understanding the molecular basis of inherited malformations of the anterior segment of the human eye that are associated with the blinding condition glaucoma. Glaucoma is the leading cause of irreversible blindness worldwide, and it is believed that 80 million people will be affected by the year 2020. Our research is now determining the early steps that lead to glaucoma with the overall goal of improving treatments for glaucoma patients.
We have shown that mutations in either the Forkhead Box C1 (FOXC1) or the Paired-like Homeobox 2 (PITX2) transcription factor genes cause Axenfeld-Rieger syndrome (ARS), a developmental disorder of the anterior segment of the eye. Approximately 75% of ARS patients develop glaucoma. Since both FOXC1 and PITX2 regulate the expression of other genes, mutations found in ARS patients disrupt the normal genetic pathway necessary for normal eye development and function. We are therefore determining the genes that are regulated by FOXC1 and/or PITX2 in the eye. We have found that mutations of FOXC1 or PITX2 results in misregulation of stress response genes, contributing to the death of key eye cells which is an important step in the development of glaucoma. We have also discovered that FOXC1 regulates the expression of genes encoding the receptors used by the medications used to treat glaucoma, and that FOXC1 mutations result in impaired ability to respond to these medications. This could provide an explanation for the drug resistant glaucoma suffered by ARS patients. We are currently determining the role of FOXC1 in export of proteins from ocular cells, and at the same time are determining what other proteins regulate the expression of FOXC1 and PITX2. The overall goal of our research is to use this information to develop new therapies to treat drug resistant glaucoma.
Walter Lab personnel
(left to right, Mr. Fahed Elian, Dr. Lance Doucette, Mr. Tim Footz, Dr. Michael Walter, Mr. Morteza Seifi, Dr. Renata Leite Ferreira de Lima, Ms. Alexandra Rasnitsyn, absent Ms. May Yu)