Antibiotic may slow or prevent diabetic retinopathy

From the Sept. 2005 edition of JDRF Research Frontline Newsletter

JDRF-funded researchers at Penn State University have found that an antibiotic used to treat acne may slow or prevent diabetic retinopathy, the most common eye-related complication of diabetes and the leading cause of adult blindness in the U.S. The drug, minocycline, has proved effective in diabetic rats and could begin tests in humans soon.

"We think minocycline could enter clinical trials relatively quickly, given that it is already FDA-approved for another use." said Thomas Gardner, M.D., director of the JDRF Center for Mechanisms and Intervention of Diabetic Retinopathy at Penn State University Hershey Medical Center, where the study was conducted.

The researchers found that minocycline reduces by half the damage caused by diabetes to certain nerve cells, microglia, in the retina. Normally, microglia act as the cleanup crew for the nervous system, disposing of damaged cells by releasing toxins and engulfing them. In the presence of diabetes, microglia in the retinas become activated inappropriately - researchers were unsure how - and release toxins that kill healthy nerve cells critical for normal vision. Treatment with minocycline blocks this activation and the ensuing nerve cell death that leads to retinopathy.

Previous studies have shown that the changes diabetes causes in the body lead to increased production of cytokines, or proteins that cause inflammation of the nerves. The Penn State study, led by Kyle Krady, Ph.D., and published in the May issue of Diabetes, goes a step further to show that in early diabetes, elevated levels of cytokines activate the microglia, setting off destruction of retinal nerve cells.

After confirming that diabetic rats had high cytokine levels, Dr. Krady treated the animals with minocycline and found that it reduced cytokine levels and inflammation. Since nerve cell damage also decreased from the drug, the study draws a strong link between elevated cytokine levels and nerve cell death, suggesting how retinal cells may be damaged or changed by diabetes.

"These results confirm that diabetes causes an early increase in the _expression of inflammatory mediators within the retina, and that minocycline reduces this inflammatory component," said study co-author Steve Levison, Ph.D, professor of neural and behavioral sciences at Penn State College of Medicine.

Dr. Gardner said the Center's data will be introduced as a candidate for therapeutic development to the Diabetic Retinopathy Clinical Research Network, a collaborative network between the JDRF and the National Eye Institute at the National Institutes of Health.

"This is an exciting new development that has great potential for the treatment of this devastating complication," said Antony Horton Ph.D., JDRF Program Director for Diabetes Complications.

Identification of minocycline's potential is the latest payoff from the JDRF Center's unconventional approach to studying diabetic retinopathy, which traditionally has been regarded as a blood vessel disease that damages capillaries supplying blood to the retina.

Researchers at the Penn State Center think retinopathy may also - or even primarily - result from changes in the retinal cells. When researchers can identify and completely understand the sequence of these early retinal changes in various cell types, the information could help medical research intervene earlier in the
course of the disorder.