Professor Michael Walter.
A team of University of Alberta researchers who discovered a gene responsible for the development of pigmentary glaucoma (PG) are now leading the charge to better understand the mechanics of how it happens.
Fighting Blindness Canada, an organization dedicated to supporting vision research in Canada, has announced a $216,300 grant to help support the work being led by Michael Walter, professor and chair of the U of A's Department of Medical Genetics. It's hoped the research will help scientists develop new therapies that can treat the disease in the future.
In 2018, an international research collaboration led by Walter identified the premelanosome protein (PMEL) gene as a gene associated with pigmentary glaucoma, shedding light for the first time on a cause for the disease. Working with Ted Allison, an associate professor of biological sciences in the Faculty of Science, the team used CRISPR Cas9 gene-editing technology to introduce the mutations into the DNA of zebrafish to model human disease, confirming effects associated with PG. The findings that linked the PMEL gene to PG were further confirmed through detection of PMEL mutations on 400 patient samples.
"All our findings together led us to conclude that PMEL mutations cause human glaucoma. However, the central question that remained was, 'But how?' How do they cause human glaucoma?" said Walter. "We know that the mutations disrupt the protein. We want to know how these mutations lead to glaucoma. Only when we understand that, can we develop new therapies to treat the disease in these patients."
PG occurs when pigments on the back of the iris get deposited into the front part of the eye and clog the eye's drainage system, which causes vision loss and could eventually lead to blindness. The disease affects hundreds of thousands of people in North America.
The new funding will allow Walter's team to study if the mutations change the structure of the PMEL molecule, and whether or not this change impacts the cells in the drainage system. Walter, a geneticist and molecular biologist, will tackle the project using two different approaches-while his lab will be using cell culture systems (modifying human cells to monitor the effects of the mutations on the cells), the collaboration with Allison's lab will continue, using the zebrafish models.
According to Walter, the project will continue to be an extensive collaboration beyond Canadian borders. While some investigators will assist by recruiting patients for additional research, biophysicists at the National Institutes of Health in Bethesda, Maryland, will join the project to study the protein properties of PMEL.
Walter is keen to continue this project and unveil the potential for future PG treatments.
"This is discovery science. It's a first step in our goal to ultimately understand PMEL better and how mutations alter PMEL, leading to disease," said Walter. "Then we can use this to develop new disease-based treatments or team-based treatments for pigmentary glaucoma. We need this information to make clinical improvements. We're not there yet, but that's where we want to go with this."
Fighting Blindness Canada is the largest private charitable funder of vision research in Canada. Over its 45-year history, it has invested more than $40 million to support vision research and education across Canada. It offers hope to Canadians by identifying the best, most promising research that is driving treatments and cures for blinding eye diseases, and by raising and stewarding funds to support essential, sight-saving research.
The project has previously received funding from the Canadian Glaucoma Research Society, Alberta Vision Network, Canadian Institutes of Health Research, Maternal and Child Health Student Support, the BrightFocus Foundation, March of Dimes Foundation, and the National Institutes of Health.