Jul 6, 2020

FBC researcher deciphering the genetic cause of pigmentary glaucoma 

Dr. Michael Walter is one of this year’s Fighting Blindness Canada (FBC) award recipients!  Dr. Walter, a professor and Department of Medical Genetics chair at the University of Alberta, received $216,300 to study a form of glaucoma called pigmentary glaucoma.

Pigmentary glaucoma occurs when pigment particles from the iris (the coloured part of the eye) are released and clog the drainage system in the eye. This causes an increase in eye pressure, which can damage the eye and lead to blindness if not treated quickly. Similar to the most common type of glaucoma, open-angle, early symptoms of pigmentary glaucoma can include peripheral (side) vision loss. However, many people with pigmentary glaucoma do not experience any symptoms at all, and because the age of diagnosis is much younger (20-40 years of age) than open-angel glaucoma it is often detected and diagnosed late – once damage to the eye has already occurred.

Dr. Walter was part of an international research team that discovered that a mutation in the premelanosome (PMEL) gene leads to some forms of pigmentary glaucoma. This is the first time a genetic cause for pigmentary glaucoma has been identified – however, we don’t know how that mutation is causing vision loss. And with funding from FBC, Dr. Walter is trying to answer this question.

In pigmented cells, such as hair, skin, and the eye, the PMEL protein forms a structure called amyloid fibrils. Dr. Walter is studying how the mutations change the shape of the PMEL protein and the amyloid fibrils. If you imagine a normal amyloid fibril as a ball of yarn, it’s as if the gene mutation causes it to unwind into a messy pile, which then clogs the eye’s drainage system and damages the cell.

This FBC-funded research project is part of a larger program of work that Dr. Walter is collaborating with other researchers on. “We are doing experiments to study the effects of PMEL mutations in the laboratory” Dr. Walter said “and at the same time we are working with scientists and physicians at the National Institutes of Health in the United States to examine patients at the earliest stages of disease. We need both laboratory and patient information to understand the disease better to get to our goal of developing better treatments.” The hope is that, taken together this research opens the door to developing new strategies to treat pigmentary glaucoma.  For instance, would fixing the structure of the amyloid fibrils prevent cells from dying? As Dr. Walter says,

“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. 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.”