Researchers Identify Gene Causing Pigmentary Glaucoma
Glaucoma is one of the leading causes of blindness around the world, and researchers are working diligently to figure out the best way to prevent and treat the condition. Despite its prevalence, not much is known about the etiology of glaucoma and understanding the causes of glaucoma is essential in effectively preventing the disease. In general, glaucoma involves an increase in intraocular pressure, which leads to compression of the optic nerve and, eventually, blindness. Unfortunately, there are usually no early warning signs when glaucoma develops, and people may not obtain a diagnosis until they have already begun to lose their vision, a process that can be slowed, but not reversed.
Recently, scientists at the University of Alberta in Canada made a breakthrough discovery about a particular type of glaucoma known as pigmentary glaucoma and provided some insight into its etiology. Pigmentary glaucoma is a result of a condition known as pigment dispersion syndrome. In people with this condition, pigment from the back of the iris, which is the part of the eye that gives it its color, is released. The pigment becomes trapped in the eye’s natural drainage systems. When pigment blocks the outflow of ocular fluids, pressure begins to build in the eye.
A Truncated Overview of Pigmentary Glaucoma and its Treatment
An eye examination should detect pigment in the eye’s drainage system and missing areas of pigment from the iris, which can raise suspicion of pigment dispersion syndrome and pigmentary glaucoma. However, clinicians have historically had a limited explanation for why this occurs in some patients. In general, the condition happens primarily among young Caucasian men who are near-sighted. Intraocular pressure may spike during exercise, which can lead to blurry vision and the appearance of halos around lights. These individuals are particularly at risk of developing glaucoma as they age.
Once patients develop pigmentary glaucoma, the treatment resembles that of other forms of glaucoma. Individuals may receive medications or surgery meant to reduce eye pressure. However, because researchers have little idea about why the iris loses pigment, it is not usually possible to reduce or stop pigmentary shedding. As a result, some researchers have focused on trying to figure out why patients lose iris pigment in the first place as a way to prevent this particular variety of glaucoma. In 2018, a team of experts at the University of Alberta in Canada, including Tim Footz, Gavin Neil and Ted Allison, along with researchers at Harvard University and Flinders University in Australia, led by Michael Walter, PhD, professor and chair of medical genetics at University of Alberta, came up with a preliminary answer. The research findings were published in the December 17, 2018, Human Molecular Genetics.
The University of Alberta Study on Pigmentary Glaucoma
The study examined two families who have demonstrated a predisposition toward pigmentary glaucoma. Members of both families underwent whole exome sequencing. The researchers found premelanosome protein (PMEL) gene to be associated with the development of pigmentary glaucoma. After identifying the particular gene, the researchers examined 400 additional patient samples, which confirmed the role the gene plays in the progression of the disease. Mutations in the gene significantly altered the composition of human cells through various biochemical and cell biology techniques.
Ultimately, the research team used CRISPR Cas9 technology to introduce mutations in the gene into the genetic code of zebrafish. The resulting specimens exhibited altered pigmentation and serious eye defects similar to human glaucoma. The findings will hopefully lead to more research on the genetic basis of pigmentary glaucoma and perhaps other forms of the disease. The University of Alberta team launched a new project designed to gain an understanding of the downstream ramifications of mutations in PMEL. Furthermore, the research uncovered potential links to neurodegenerative diseases such as Alzheimer’s disease, which are other research routes.
Potential Clinical Applications of the New Research
While the direct clinical applications of the new discovery are likely years, if not decades, away, they may begin benefiting some individuals much sooner. In families with a propensity for pigmentary glaucoma, it is possible for family members to undergo exome sequencing to show if they have mutations in the PMEL gene. While not having a mutation does not guarantee an individual will never have the disease, finding a mutation means regular eye exams are extremely important to catch the disease in its earliest stages and to be connected to vision-saving interventions.
The potential connection between glaucoma and neurodegenerative conditions such as Alzheimer’s disease also opens the door to new treatment options. As researchers explore this connection more fully, they may discover how neurological treatments can be applied directly to ophthalmology or shifted in a such a way to help to treat glaucoma. The research also creates a strong case for launching new studies on the genetic underpinnings of other forms of glaucoma.
