For the first time, a cause behind pigmentary glaucoma—one of the leading causes of blindness in adults—has been revealed by a global team of researchers from the University of Alberta, Harvard University and Flinders University in Australia.
The breakthrough research began three years ago with an Edmonton family that has a running history of the eye disease, and has since spiraled into an international research effort involving more than 400 patients with pigmentary glaucoma.
Patients with a PMEL gene mutation are encouraged to do routine screenings that can detect the development of pigmentary glaucoma, thanks to the breakthrough research that identified the mutation as a root cause of the disease.
The result? A discovery of a gene mutation that researchers have identified as the root cause of the disease, paving the way for early detection and the possibility of new treatment methods for glaucoma.
“Often by the time glaucoma is detected, you already have vision loss,” said Michael Walter, a medical genetics professor at the University of Alberta and lead author of the study. Walter said people over the age of 80 have a one in 10 chance of developing glaucoma, a disease that involves the malfunction of the optic nerve, which links the eyes to the brain.
“As our population ages, it becomes increasingly important to identify the causes of it,” Walter said.
There are many distinct forms of glaucoma, but Walter’s research focuses on pigmentary glaucoma, which affects between 150,000 and 300,000 people in North America, and has an early onset in people who are in their 20s or 30s, versus other forms of glaucoma which surface later on.
This particular form of the disease involves the breakdown of pigment, or melanin-holding cells that are located in the back of the iris (the colored part of the eye). The breakdown causes an overflow of fluid in the eye, which increases pressure on the optic nerve and causes it to malfunction.
Walter says it’s akin to a “plumbing problem” and that researchers had little idea about the root causes behind it.
“We could see the disease in patients, but we didn’t know why they were developing it,” Walter said. This posed challenges in both detecting the disease before irreversible vision damage was done to the eye, and also with effectively treating it.
But after combing through several terabytes of complex genetic data of patients with pigmentary glaucoma, as well as of their family members who are vulnerable to developing the disease, Walter and his team were able to identify a mutation in one part of the pigment cell, the premelanosome protein (PMEL), as the reason behind the development of the eye disease.
This was confirmed by additional samples of patients, all of whom had a PMEL gene mutation, and the introduction of the mutation into the DNA of zebrafish, who began to develop symptoms of glaucoma as well.
Walter said it’s not yet known if everyone born with a PMEL mutation will develop the disease later on, but linking pigmentary glaucoma to the mutation means those who with the mutation will know to do regular screening tests that may detect the disease before irreversible damage is done to their vision, and commence effective treatment methods like eye drops or surgery if necessary.
The research, funded partly by the Royal Alexandra Hospital Foundation, as well as several provincial, national and international groups, will now pave the way for further work on developing new types of treatment for patients with pigmentary glaucoma, Walter said.
He added the collaboration between Harvard, the University of Alberta and Flinders University made the breakthrough discovery possible, as the institutions, who were already doing similar research separately, were able to share brain power and resources.
“It’s easier to collaborate than to compete,” Walter said.
