Team 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.”