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Role Identified For Glaucoma Gene And Related Signaling Pathway

Date:
February 18, 2008
Source:
University of Iowa
Summary:
Researchers have found that 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. The study, which revealed that over-expression of the gene, sFRP1, elevates pressure in the eye, could help improve glaucoma diagnosis and lead to the development of sight-saving treatments.

Researchers have found that 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. The team was led by Alcon Research and included investigators from the University of Iowa and the National Cancer Institute (NCI), part of the National Institutes of Health.

The study, which revealed that over-expression 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," said Abe Clark, Ph.D., 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."

Glaucoma is the second leading cause of irreversible blindness in the United States 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 is often 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," said study team member John Fingert, M.D., Ph.D., assistant professor of ophthalmology and visual sciences at the UI Roy J. and Lucille A. Carver College of Medicine.

Jeffrey Rubin, M.D., Ph.D., at NCI's Center for Cancer Research, who was involved in the study, had previously discovered the sFRP1 gene. The team compared the genes that are expressed in the eyes of people with glaucoma to 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 both human donor eyes and mouse eyes. When the investigators delivered sFRP1 protein to the eyes, the pressure in these eyes became elevated.

The results suggest that over-expression 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 reduced high pressure in mouse eyes (this was not tested in human donor eyes).

"We are hopeful that further study of sFRP1 and the WNT-signaling pathway will help advance our understanding of why some people get glaucoma and others do not," Fingert said.

The study, Increased expression of the WNT antagonist sFRP-1 in glaucoma elevates intraocular pressure, appeared online Feb. 14 in the Journal of Clinical Investigation. In addition to Clark, the Alcon scientists involved in this discovery included Wan-Heng Wang, Ph.D., Loretta McNatt, M.S., Iok-Hou Pang, Ph.D., Cameron Millar, Ph.D., Peggy Hellberg, M.S., Mark Hellberg, Ph.D., Tom Steely, Ph.D.

In addition to Fingert, other UI researchers involved in the study included Val Sheffield, M.D., Ph.D., the Martin and Ruth Carver Chair in Genetics, professor of pediatrics and a Howard Hughes Medical Institute (HMMI) investigator; and Edwin Stone, M.D., Ph.D., the Seamans-Hauser Chair of Molecular Ophthalmology, professor of ophthalmology and visual sciences, and an HHMI investigator.

The study was funded by Alcon Research, based in Fort Worth, Texas.


Story Source:

The above story is based on materials provided by University of Iowa. Note: Materials may be edited for content and length.


Cite This Page:

University of Iowa. "Role Identified For Glaucoma Gene And Related Signaling Pathway." ScienceDaily. ScienceDaily, 18 February 2008. <www.sciencedaily.com/releases/2008/02/080214191447.htm>.
University of Iowa. (2008, February 18). Role Identified For Glaucoma Gene And Related Signaling Pathway. ScienceDaily. Retrieved September 2, 2014 from www.sciencedaily.com/releases/2008/02/080214191447.htm
University of Iowa. "Role Identified For Glaucoma Gene And Related Signaling Pathway." ScienceDaily. www.sciencedaily.com/releases/2008/02/080214191447.htm (accessed September 2, 2014).

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