"Blindness" gene finally identified.

A gene and a related signaling pathway play a role in the development of glaucoma, which is a common cause of visual impairment and blindness worldwide, it has been found by scientists led by Alcon Research, Ft. Worth, Tex., and including investigators from the University of Iowa, Iowa City, and the National Cancer Institute, Bethesda, Md. The study, which revealed that overexpression of the gene sFRP1 elevates pressure in the eye, could help improve glaucoma diagnosis and lead to the development of sight-saving treatments.

"The cause of glaucoma and the resulting elevation of intraocular pressure has been poorly understood," relates Abe Clark, Alcon's vice president of discovery research and head of glaucoma research. "This new discovery may allow researchers to develop therapies to treat the underlying cause of the disease."

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Glaucoma is the second leading cause of irreversible blindness in the U.S. (hypertension is number one) and the leading cause among African-Americans. The disease damages the optic nerve, which connects the eye to the brain, and leads to vision loss, especially peripheral vision. High pressure in the eye often is related to this nerve damage and vision loss.

"Although there have been leaps and bounds in glaucoma research, we are just beginning to understand the causes of high pressure in the eye and nerve damage that leads to vision loss in glaucoma," says study team member John Fingert, assistant professor of ophthalmology and visual sciences at Iowa.

Jeffrey Rubin at NCI's Center for Cancer Research, who was involved in the study, had discovered the sFRP1 gene previously. The team compared the genes that are expressed in people with healthy eyes. They saw that some genes, including sFRP1, are much more active, or "expressed," in cells from eyes with glaucoma.

sFRP1 is part of a signaling pathway involving a series of other genes known as the WNT-signaling pathway. The team tested the effects of the gene on the pressure in human donor eyes. When the investigators delivered sFRP1 protein to the eyes, the pressure in these eyes became elevated. The results suggest that overexpression of sFRP1 disrupts the WNT-signaling pathway and seems to cause glaucoma's hallmark high pressure in the eyes. In addition, the team found that applying a substance that normalizes the WNT-signaling pathway significantly reduces that high pressure.