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Scientists Spot Gene That Causes Glaucoma

by VR Sreeraman on February 19, 2011 at 9:02 PM
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 Scientists Spot Gene That Causes Glaucoma

Researchers have identified a new candidate gene for the most common form of glaucoma, primary open angle glaucoma (POAG).

The findings offer novel insights into glaucoma pathology and could lead to targeted treatment strategies.

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Glaucoma - a leading cause of vision loss and blindness worldwide - runs in families.

So far, three genes have been associated with human glaucoma, but they account for only a small fraction of cases and have not shed much light on the disease process.
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A team of investigators from Vanderbilt University and the University of Florida turned to a model with simpler genetics-a canine model of the disease.

Forty years ago, Kirk Gelatt, from the UF College of Veterinary Medicine, came across a litter of beagles that had a high incidence of glaucoma. The finding suggested to Gelatt that the disease was inherited, and he established a colony of POAG-affected beagles to study treatments for the disease.

In affected beagles, intraocular pressure begins to increase at 8 to 16 months of age, due to increased resistance to aqueous humor outflow. The clinical course of the disease "absolutely resembles human glaucoma," said Rachel Kuchtey, principal investigator of the study.

The researchers used blood samples to search for genes associated with POAG. They first narrowed in on a certain spot (locus) on canine chromosome 20, which matched part of human chromosome 19. Previous studies had associated the human region with intraocular pressure, a good sign that they were on the right track, said John Kuchtey, first author of the study.

Sequencing of the entire canine locus revealed that a gene called ADAMTS10 was the strongest disease-associated candidate. POAG-affected dogs have a single mutation in the gene, which encodes a protein involved in processing the extracellular matrix (ECM), the connective and structural support tissue around cells.

"There is a lot of evidence that proteoglycans (molecules in the ECM) and matrix remodeling might have something to do with aqueous outflow resistance, and so this gene supports that line of investigation," said John.

The researchers also demonstrated that the gene is highly expressed in the trabecular meshwork-the specialized filtration tissue through which aqueous humor passes, another supportive piece of evidence that it may have a role in regulating aqueous humor outflow.

The findings have been reported in the journal PLoS Genetics.

Source: ANI
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