An international team of researchers has identified a gene responsible for the appearance of pigmentary glaucoma, which may lead to new therapies for the disease.
"People who have traditionally not thought about having glaucoma – young men in their 20s and 30s – are particularly at risk from this form of the disease and from losing sight," said Michael Walter, professor and chief of medical genetics at the hospital. University of Alberta.
It is the first time that a cause of the disease has been identified.
Pigmentary glaucoma (PG) occurs when the pigment at the back of the iris is deposited on the front of the eye, causing vision loss and eventually blindness if left untreated. It is estimated that at least 150,000 people in North America are affected by the condition.
The study, led by Walter, also involved researchers from Harvard University and Flinders University in Australia. The team, using data from two individual families with a predisposition to PG, used a technique known as complete exome sequencing to identify the premelanosome protein (PMEL) gene as an associated with pigmentary glaucoma. The finding was further confirmed by the detection of more mutations of the PMEL gene after the examination of 400 additional patient samples.
The researchers determined that mutations in the PMEL gene had biological consequences, using a series of biochemical and cell biology tests to show that most mutations significantly altered human cells. Collaborating with Ted Allison, associate professor of medical genetics at U of A, the team used the gene-editing technology called CRISPR Cas9 to introduce mutations into zebrafish DNA.
"We found that these fish had altered pigmentation and ocular defects reminiscent of human glaucoma," Walter said. "Overall, the findings have clearly shown that we have identified a new gene that causes glaucoma.
"I think the collaborative effort we've had in this research has allowed us to explore this more fully than any lab could have done."
Walter, who is also a member of Alberta Vision Net, which brings together researchers from Alberta and Calgary universities to promote understanding and treatment of eye disease, is now focused on efforts to better understand how mutations lead to pigmented glaucoma. He said the research also identified unexpected similarities with other neurodegenerative diseases, such as Alzheimer's disease, which could lead to new possibilities for treatment.
"It opens up awareness of other approaches we can take," Walter said. "Potentially, some of the methods currently being used to think about the treatment of Alzheimer's disease may even be applied in the treatment of glaucoma."
The research was published in Human Molecular Genetics.
Researchers use CRISPR engineering to prevent certain glaucoma in mice
Adrian A Lahola-Chomiak et al, non-synonymous variants in premelanosome protein (PMEL) cause dispersion of the ocular pigment and pigmentary glaucoma, Human Molecular Genetics (2018) DOI: 10.1093 / hmg / ddy429
University of Alberta School of Medicine and Dentistry
Scientists first to identify a cause of pigmentary glaucoma (2019, January 31)
recovered on January 31, 2019
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