Gene mutation uncovers potential treatment for rare form of pediatric glaucoma

A mutation in a gene called TEK, may hold the key to treating a rare and severe form of glaucoma in young children, according to researchers at Northwestern University Feinberg School of Medicine and the University of Wisconsin-Madison.

The finding, "Angiopoietin receptor TEK mutations underlie primary congenital glaucoma with variable expressivity," appeared June 6 in the Journal of Clinical Investigation.

The gene, TEK, aids in the development of a drainage channel in the eye called Schlemm's canal. The canal drains fluid from the eye's anterior portion. In individuals with glaucoma, this channel may not be working or is absent altogether, so pressure builds up and damages the optic nerve, resulting in vision loss.

In the new study, the mutated TEK gene, identified by the same researchers in mice two years ago, was discovered in 10 families by screening and testing 189 families with a history of primary congenital glaucoma (PCG). The TEK mutations in those 10 families showed "an interruption in cellular signaling needed in the development of the canal." Mutations were not found in other genes linked to causing glaucoma.

Susan Quaggin, M.D., one of the lead researchers and chief of nephrology and hypertension at Northwestern University Feinberg School of Medicine and Northwestern Memorial Hospital, says in an article online, "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."

"This is an important step in learning more about the biology of general glaucoma as well—a devastating eye disease that impacts more than 60 million people worldwide," says co-lead researcher Terri Young, M.D., chair of the department of ophthalmology and visual sciences at the University of Wisconsin School of Medicine and Public Health.

One in every 10,000 infants is born with PCG from birth to three years of age, according to The Glaucoma Foundation. Untreated, it can result in childhood blindness. The cause of PCG had not previously been identified. Researchers are now working on an eye drop that could treat PCG.

According to the researchers, PCG is expressed by:

• Infant/early-childhood ocular hypertension
• Enlarged eye globes (buphthalmos)
• Optic neuropathy

Doctors of optometry say the finding is promising

"This is another step regarding the use of genetic information to create new therapies that would directly treat the underlying problem and get structures to develop fully," says Murray Fingeret, O.D., chief of optometry at the U.S. Department of Veterans Affairs, New York Harbor Healthcare System, in Brooklyn, New York. Dr. Fingeret is the first and only doctor of optometry appointed to the Board of Directors of The Glaucoma Foundation, where he continues his life's work of research and collaboration into finding a cure.

Doctors of optometry should be prepared to share this development with parents, especially if they have a family history of congenital glaucoma, he says.

"The findings have two implications," Dr. Fingeret says. "First, when a specific genetic test is available in the future, it would allow mothers who may be at risk (due to a family history) to have the test performed."

He adds, "Second, the exciting news this study presents is, if you know where the genetic mutation is exactly, genetic therapies can be targeted at this gene to get it to perform differently. For instance, genetic therapy would allow the drainage system in the newborn to develop properly."

Marie Bodack, O.D., chief of pediatric primary care at Southern College of Optometry in Memphis, Tennessee, agrees. Dr. Bodack has lectured nationally and internationally on various subjects including pediatric eye disease, vision therapy, amblyopia and reading problems. 

"This research is promising in terms of developing potential treatments for this condition," Dr. Bodack says. "Novel treatments may be developed to allow for better visual outcomes and fewer surgeries for these children. Gene therapies also may be able to target the defective gene to allow for normal anterior segment structure development."

She adds, "Even with the potential for new treatments, it is important that parents bring their children in for eye examinations during infancy so that problems such as congenital glaucoma can get detected and treatment initiated at an earlier time."

The AOA follows all research closely, including potential treatments for glaucoma; however, more research is needed regarding the influence of gene therapy on visual health.