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UI researchers identify gene that causes common form of glaucoma
IOWA CITY, Iowa -- Researchers at the University of Iowa College of
Medicine have identified a gene responsible for primary open angle glaucoma,
the most common form of glaucoma and the second leading cause of legal
blindness in the United States.
In an article published in the Jan. 31 issue of the journal Science,
UI researchers, led by Drs. Edwin Stone, associate professor of ophthalmology,
Val Sheffield, associate professor of pediatrics, and Wallace L. Alward,
professor of ophthalmology, report that mutations in a gene located on
chromosome 1 are responsible for primary open angle glaucoma. The UI team
had linked this form of glaucoma to chromosome 1 in a separate study three
"These study results point to the potential availability of a blood
test that can identify people at risk for primary open angle glaucoma,"
says Dr. Thomas Weingeist, UI professor and head of ophthalmology. "Therefore,
more attention can be paid to following these patients and perhaps treating
them earlier. It also means that it may be possible to identify drugs that
can be more effective in treating this disease."
Glaucoma is a condition in which loss of vision is characterized by
the degeneration of the optic nerve, usually associated with increased
pressure within the eye. This increased pressure can be caused by problems
in the eye's trabecular meshwork, which filters the watery fluid, known
as the aqueous humor, that bathes the inside chamber of the eye behind
the cornea and in front of the lens.
"In 1993 we studied a large family with a history of glaucoma and
identified a region of chromosome 1 to be associated with juvenile open
angle glaucoma, which is a subset of primary open angle glaucoma and occurs
at an earlier age," Stone says. "Studies by other researchers
subsequently identified additional families that mapped to this region.
For this study, we used genetic linkage analysis and shared genetic information
among the families to further narrow that area on chromosome 1."
Several genes that mapped to this region of chromosome 1 were considered
by the UI researchers as the glaucoma-causing gene. The researchers determined
that one gene in particular -- known as the TIGR gene -- existed within
this region and was known to be expressed in the trabecular meshwork and
ciliary body of the eye, both of which are involved in the maintenance
of the intraocular pressure.
Stone, Sheffield, Alward and their colleagues studied eight families
they suspected had gene mutations at this specific area on chromosome 1,
including the original family that allowed UI researchers to identify chromosome
1 three years earlier. Of the eight families, the UI team found three different
TIGR gene mutations among four of those families.
"At that point we could say that this gene causes a type of inherited
glaucoma in families in which the disease gene can be shown to map to chromosome
1," Sheffield says. "But perhaps this is only one-tenth of one
percent of all glaucoma. So, the next step was to determine if the gene
was also mutated in some unrelated patients with glaucoma."
The UI team studied 227 unrelated glaucoma patients with a family history
of the disease and 103 unselected, or "walk-in," primary open
angle glaucoma patients seen at a single clinic. Of the 227 patients with
a family history of the condition, 10 (nearly 4.5 percent) had one of the
three TIGR gene mutations. Of the 103 unselected patients, 3 (about 3 percent)
harbored one the three TIGR gene mutations.
"These findings suggest that this gene plays a role in a portion
of all primary open angle glaucoma," Stone says. "When you consider
that glaucoma affects between 2.5 and 5 million people in the United States,
the 3 percent we found in the unselected patients group suggests that mutations
in the TIGR gene cause glaucoma in more than 100,000 people."
The identification of the gene for primary open angle glaucoma will
help researchers better understand the disease, which could lead to better
treatments. "The TIGR gene is believed to cause increased pressure
in the eye by obstructing the outflow of the aqueous humor, the fluid that
bathes the inside of the eye," Alward says. "Now it's possible
to examine whether the mutations we describe in this study play a role
Identifying the TIGR gene also increases the possibility of developing
accurate testing for genetic predisposition to glaucoma before symptoms
arise. "Open angle glaucoma can be treated with existing drugs or
surgery in most cases," Alward says. "Discovering specific glaucoma-causing
mutations will make it possible to identify patients at risk for this disease
before significant visual loss has occurred."
The UI study was funded through grants from the National Eye Institute
of the National Institutes of Health, the Roy J. Carver Charitable Trust
and the organization Research to Prevent Blindness. The UI Research Foundation
is seeking patent protection for the UI team's body of research.