CardiovascularTeam Discovers Gene For Age-Related Cataracts
Participants in the University of Wisconsin-Madison"s
long-running Beaver Dam Eye Study have contributed to the discovery of a
gene involved in cataracts in both aging humans and in mice.
In a paper published July 30 in the online Public Library of Science
Genetics journal, an international team of researchers announced that it
has pinpointed a human gene, EPHA2 - and its mouse counterpart - that
appears to be linked to older people developing cortical cataracts.
Age-related cataracts cloud the lens of the eye with opaque proteins and
cause 18 million cases of blindness and 59 million cases of reduced vision
worldwide. By age 65, about a quarter of all Caucasian Americans will have
developed cataracts.
"It looks like we have found a gene in common with age-related cortical
cataract, one of the three most common age-related cataract types, in
several different human populations and in two different "knockout" mouse
models," says Barbara Klein, professor of Ophthalmology and Visual
Sciences in the UW-Madison School of Medicine and Public Health.
Klein and her husband and research partner, Ronald Klein, also a
UW-Madison ophthalmology and visual sciences professor, created and lead
the Beaver Dam Eye Study, which has been following the eye health of
nearly 5,000 Beaver Dam, Wisconsin residents since 1988. Along with lead
author Sudha Iyengar of Case Western Reserve University School of
Medicine, the two are co-authors of a paper written by scientists in the
United States, England and Australia who worked together to find the gene.
Genetic analysis of several hundred of the Beaver Dam participants showed
that a mutant version of the EPHA2 gene was present in families that
tended to develop cortical cataracts as family members age. Scientists
believe that the normal gene maintains lens clarity while the mutant
variations produce proteins that cloud the lens. A similar association was
found among British families and in families living in the Blue Mountains
of Australia - suggesting that scientists had discovered the key human
gene for cortical cataracts.
Meanwhile, Case Western Reserve scientists developed two strains of mice
that have a mutant gene that leads to the development of cataracts in
mice.
"This is very fortuitous because it may provide a useful animal model to
understand how cortical cataracts develop in humans and how to alter that
development," Klein says. Other genes, especially those involved in
oxidative stress, diabetic complications, neurodegenerative diseases, and
the metabolism of certain elements may also play a role.
Ophthalmologists have long known that, along with age, female gender,
diabetes, hypertension and history of smoking, UV light exposure and heavy
alcohol intake, are all risk factors for developing cataracts.
Barbara Klein noted that discoveries such as this one are a tribute to
"the wonderful community spirit" of the people of Beaver Dam, a city of
about 15,000 people northeast of Madison. She says the Beaver Dam Eye
Study has produced about 300 scientific papers on new discoveries.
"Beaver Dam has been an incredible place to work," she says. "Large
population-based studies like this one are getting harder and harder to do
because people are too busy and don"t seem to have the same community
spirit that exists in the participants in the Beaver Dam Eye Study."
University of Wisconsin-Madison