Breakthrough Pinpoints Cause of Pigmentary Glaucoma

A breakthrough discovery by an international team of researchers has identified the gene that causes pigmentary glaucoma (PG), paving the way for the potential development of new treatments for the condition.

The team, headed by University of Alberta chair of medical genetics Professor Michael Walter, along with fellow researchers from Harvard University in the US and Flinders University in Australia, found that the premelanosome protein (PMEL) gene is associated with PG.

The team used whole exome sequencing on data from two families predisposed to PG to make the discovery. Their findings were confirmed by detecting more PMEL gene mutations in 400 other patient samples.

The researchers found that the PMEL gene mutations had biological consequences based on a series of biochemical and cell biology tests, where they determined most of the mutations significantly altered human cells.

Using the gene-editing tool CRISPR Cas9 the team introduced the mutations into the DNA of zebrafish, which also developed symptoms of glaucoma.

“We found that these fish had altered pigmentation and eye defects which were very reminiscent of human glaucoma,” Walter said.

“Altogether, the findings showed us quite clearly that we have identified a new gene that causes glaucoma.”

Walter pointed out it is not known whether everyone born with a PMEL mutation could develop the condition late in life, but establishing the link of PG with the mutation would qualify people with the gene to take regular screening tests to detect the condition early on and prevent it from causing irreversible vision damage.

“People who traditionally we wouldn’t think of having glaucoma, young males in their 20s and 30s, are at particular risk for this form of the disease and of losing their vision,” Walter said.

“It opens up awareness about other approaches we could take. Potentially some of the methods that are currently being used to think about treating Alzheimer’s might even be applied to treat glaucoma,” Walter added.

The findings were published in the journal Human Molecular Genetics.