Perspectives Online

Researchers receive $2 million from NIH to study genetics of glaucoma

What Dr. Robert Anholt learns from his research on the Drosophila eye model is leading to studies of genes associated with or predictive of the development of glaucoma in humans.
Photo by Daniel Kim

N.C. State University scientists have received $2 million from the National Institutes of Health to study the genomics of glaucoma, the second leading cause of blindness. Glaucoma affects 50 to 60 million people worldwide.

Dr. Robert Anholt, professor of zoology and genetics and director of N.C. State's Keck Center for Behavioral Biology, says the four-year project with the National Eye Institute will allow researchers from N.C. State and UNC-Chapel Hill to use the model organism Drosophila melanogaster - the fruit fly - to identify potential genes that may convey susceptibility to glaucoma.

Glaucoma is progressive degeneration of the optic nerve. The disease causes increasingly blurred peripheral vision leading to tunnel vision and eventually blindness. One of every 100 people over the age of 40 has glaucoma, and rates for African-American and Hispanic populations are especially high.

The most effective glaucoma treatment currently practiced is slowing down the disease by lowering or relieving pressure in the eye, Anholt says; there are no available treatments for reversing or eradicating glaucoma.

"We don't know if pressure in the eye is causative or correlative since pressure can vary in different people," Anholt says. "In this study, we're looking for better predictors for who is at risk and for improved diagnostics so people can preserve vision longer."

The research effort results from an early discovery in the Anholt lab of a protein named olfactomedin. A groundbreaking 1997 finding by California researchers linked mutations in a protein called myocilin, which is homologous to olfactomedin, with incidences of congenital glaucoma in humans. This gave researchers the first molecular handle on glaucoma, Anholt says.

Using D. melanogaster as a model, Anholt and fellow researchers in 2003 overexpressed the myocilin protein in fly eyes. The results, published in the journal Genetics, showed fluid discharge resulting from increased pressure in the eye, which is often a prelude to glaucoma.

Anholt and colleagues then wanted to find out if other proteins were altered in flies when myocilin was overexpressed. They found that a new, neurodegenerative protein discovered in D. melanogaster, nicknamed "swiss cheese" because mutants develop brain lesions, showed increased activity.

Anholt's team and Dr. Teresa Borras, formerly of Duke University and now at UNC-Chapel Hill, tested overexpression of the myocilin protein in post-mortem human eyes. The homolog for "swiss cheese" - called neuropathy target esterase - showed increased activity when myocilin was overexpressed in post-mortem human eyes.

With the new funding, Anholt and his colleagues plan to incorporate human subjects into the study.

- NCSU News Services

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