New Perspectives on Vision Research

Collaboration is the key as Kellogg's newest research team drives toward treatment for diabetic eye disease

Thomas W. Gardner, M.D., M.S., Steven F. Abcouwer, Ph.D., and David A. Antonetti, Ph.D. in the new Kellogg Eye Center

It was not an easy decision for three senior scientists and another six associates to move their research program to the University of Michigan Kellogg Eye Center. But as Thomas W. Gardner, M.D., M.S., describes it, the pieces fell into place as the team began to see that Michigan offered a welcoming culture where scientists embraced collaboration and the unique style of inquiry that is at the heart of their work on diabetic retinopathy.

Dr. Gardner, along with Steven F. Abcouwer, Ph.D., and David A. Antonetti, Ph.D., is part of a dynamic team whose goal is to understand how diabetes inflicts damage on the retina and then to use their findings to develop better treatments for the disease. Says Dr. Gardner, "A guiding principle for each of us is that the results of basic research should be used to help patients now."

The challenge is formidable. Today diabetes affects nearly 24 million people, and another 57 million have pre-diabetes. By 2050, one in three Americans will have diabetes, according to a new report from the Centers for Disease Control. Scientists at the Kellogg Eye Center are driven by the knowledge that diabetes-related eye disease is the leading cause of irreversible blindness among adults.

Cheng-mao Lin, Ph.D., Assistant Research Scientist, with lab staff members Mandy Losiewicz, Jason Keil, and Sumathi Shanmugam, all part of the new diabetic retinopathy research team.

Diabetes affects the blood vessels in the eye, resulting in observable changes characterizing a condition known as diabetic retinopathy. The blood vessels become leaky, leading to retinal swelling, and eventually produce fragile, brush-like branches and scar tissue. The result is blurred or distorted vision that can lead to blindness if not promptly treated.

Because damage to the blood vessels figures so prominently in diabetic retinopathy, many scientists focus their research solely on the vasculature of the eye. Dr. Gardner and his team prefer, instead, to talk in terms of the "whole retina:" the neurons that form vision by sending light converted into electrochemical signals to the brain; glial cells that support the metabolism of the neurons and perform immune functions; and the system of blood vessels that are the most visible signs of the disease.

Dr. Gardner sees patients in Kellogg's Retina Clinic and conducts clinical trials as well as directing a research laboratory. He investigates changes in the retina's neural tissue and the features of diabetic retinopathy that cause neurons to die. That perspective allows new strategies to surface. "When you view diabetic retinopathy as a neuro-degenerative disease, you begin to see that other classes of drugs could be effective in combating it," says Dr. Gardner.

One example is doxycycline, a drug also being tested for Parkinson's disease. After promising results in animal models, Dr. Gardner and his team initiated a clinical trial to see whether the drug could reduce the loss of vision in individuals with diabetic retinopathy. Results from the study are expected in less than two years.

Another promising treatment model is emerging from Dr. Antonetti's laboratory. He has discovered a small drug inhibitor that blocks a protein well known to scientists—vascular endothelial growth factor or VEGF. This protein weakens the blood–retina barrier, a tightly sealed structure that protects the retina. The discovery of the inhibitor came from Dr. Antonetti's study of mechanisms involved in the formation and breakdown of this important barrier. Now his lab is engaged in"medicinal chemistry," fine-tuning the drug candidate in hopes of moving it toward clinical testing.

A third tack comes from Dr. Abcouwer's lab, with its focus on the role of glial cells in diabetic retinopathy. Glia help maintain the well-being of other retinal cells. Innate immune cells called microglia constantly monitor the retinal environment, extending arm-like projections into the neural tissue and vasculature that his colleagues study. "These cells undergo distinct changes during the course of the disease, but it is not clear whether the changes are beneficial or detrimental," he says.

The three investigators pursue their own areas of specialty, but they are a fluid group, pairing up in various combinations to launch promising new projects."The glue that holds us together is our common interest in the disease, despite our different perspectives," observes Dr. Antonetti.

How will this approach play out at Kellogg? Very smoothly, the scientists agree. "Kellogg has a strong group of basic scientists exploring retinal degeneration and regeneration, the same kinds of problems we are investigating," says Dr. Gardner. Then we have a major diabetes research program in the same building. Dr. Gardner had just returned from a meeting with the Brehm Coalition, scientists who employ the kind of broad-based inquiry that is familiar to his team. And finally, says Dr. Gardner, we have people at Michigan who are experts in the other complications of diabetes. "Michigan has a unique blend of talent that you would be hard pressed to find almost anywhere else."

Not surprisingly, the promise of collaboration among diabetes researchers was a frequent theme during the building campaign. Department Chair Paul R. Lichter, M.D., who recruited the team from Penn State University, saw the possibilities early on. "It stands to reason that this critical mass of world-class scientists is sure to discover new ways to fight the devastating ocular complications of diabetes."