By Michael Haederle

Visionary Research

UNM Scientists Share in $2.8 Million Grant Targeting Diabetic Retinopathy

The burden of diabetes weighs far more heavily on New Mexicans than on most Americans. Forty percent of the state's residents suffer from the full-blown disease - or its precursor, prediabetes - and many of them are at risk for retinopathy, a leading cause of blindness.

UNM's Arup Das, MD, PhD, Regent's Professor in the Division of Ophthalmology, and his long-time collaborator, Paul McGuire, PhD, a professor in the Department of Cell Biology and Physiology, will share in a five-year, $2.8 million grant from the National Eye Institute to explore the genetic differences that make some diabetes patients more likely to experience retinopathy - and who is most likely to benefit from existing treatments.

"This study will show us if there's a genetic factor that explains who responds well to the drugs and who doesn't," says Das, who is the grant's principal investigator. He and McGuire hope that their research will yield insights that lead to more effective medications.

New Mexico has 241,000 diabetics - 14 percent of the population, Das says. Another 600,000 have prediabetes, and the disease costs the state about $2 billion a year in medical expenses and lost productivity. Das estimates that 35 to 45 percent of diabetic patients have retinopathy and related blindness - and many of them come to him for treatment.

"The first question I face as a clinician is, 'Am I going to be blind?'" Das says. "This is a question I face in the clinic every day."

Retinopathy - a condition in which the light-sensing tissue at the back of the eye deteriorates - is highly unpredictable. It's an inflammatory process that starts with swelling called macular edema and then progresses to the point where new blood vessels sprout and start hemorrhaging, causing retinal detachment.

Many diabetics will not develop progressive diabetic retinopathy during their lifetime, Das says, pointing out that some patients might have diabetes for 30 years with no vision loss.

"They are somehow protected," Das says. "There must be some genetic factors that are keeping them from getting these complications in the eye. If we can find out those factors, maybe we can discover what is causing diabetic retinopathy and come up with new treatments."

The Diabetic Retinopathy Genetics Study is a multi-center, multi-ethnic grant that also includes the Translational Genomics Research Institute, a Phoenix-based organization that conducts genomic research, and the Joslin Diabetes Center, a Harvard-affiliated group in Boston, McGuire says.

The UNM and Joslin teams will collect DNA samples and medical histories from diabetic patients, while the Phoenix researchers will conduct genomic sequencing," he says.

"One gene we've recently identified in people who develop retinopathy and people who don't is a gene that is important in normally regulating new blood vessel formation in the eye," he says. "It looks like a mutation in that gene might prevent the formation of a factor that's important in inhibiting new blood vessel formation."

The researchers suspect that the mutation lies dormant until diabetes symptoms appear. "We're about to start screening populations for that mutation and then correlating that with the history of their disease," McGuire says, "A lot of the early work is going to be correlating physical findings with genetics, with responses to treatment."

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