Gene linked to cause of blindness in kids

Scientists have identified a gene that causes severe glaucoma in children and say the finding could lead to future therapies to treat the disease, which currently has no cure.

“This work shows us how a genetic mutation causes a severe form of glaucoma called primary congenital glaucoma, which afflicts a significant portion of children enrolled in institutions for the blind worldwide,” says principal investigator Susan Quaggin, chief of nephrology and hypertension at Northwestern University Feinberg School of Medicine and Northwestern Memorial Hospital.

The gene called TEK is involved in the development of a vessel in the eye called Schlemm’s canal, which drains fluid from the anterior portion of the eye. In glaucoma, this vessel can be defective or missing, creating pressure buildup that can damage the optic nerve and cause vision loss.

In a previous study, Quaggin showed that deleting the gene in mouse models led to glaucoma, but she didn’t know how mutations impairing the gene affected humans.

After publishing the earlier research, Quaggin met with Terri Young, a pediatric ophthalmologist at the University of Wisconsin-Madison, who had identified mutations in TEK in some of her patients, but didn’t know the significance.

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“It was more than coincidental,” Quaggin says, adding that scientists then identified more mutations of the gene in children with primary congenital glaucoma. “It was one of those eureka moments that sometimes happens in science.”

Altogether, scientists found TEK mutations in 10 unrelated families with children who have primary congenital glaucoma. All of the children did not have mutations in other genes known to cause glaucoma.

Findings made in animal models don’t always translate to patients, but the new study, published in the Journal of Clinical Investigation, shows that TEK mutations identified in children impair the vascular signaling pathway important in Schlemm’s canal formation—just like they do in mice.

“We don’t know how other genes associated with glaucoma cause this disease,” Quaggin says. “With TEK, we know exactly what’s going wrong, which means we’ve identified a pathway that could be a great new therapeutic target for severe glaucoma and even more common forms of the disease.”

Quaggin’s group is developing an eye drop that repairs the TEK pathway to fix the faulty vessel and is also exploring whether TEK pathway mutations play a role in adult-onset glaucoma.

The National Institutes of Health, the Research to Prevent Blindness Inc. Lew R. Wasserman Award, the Duke–National University of Singapore Core Grant, the University of Wisconsin Centennial Scholars Award, the March of Dimes Foundation, Howard Hughes Medical Center, Ophthalmic Research Institute of Australia, Channel Seven Children’s Research Foundation, and the National Health and Medical Research Council of Australia funded the work.

Source: Northwestern University