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Researchers Discover Link between Hyperglycemia and Retinopathy

Posted: Tuesday, January 24, 2006

Research explains how methylglyoxal (MG), a glucose-derived molecule that is overproduced in cells damaged by hyperglycemia, turns on a gene called angiopoietin-2, which plays a central role in the loss of small blood vessels in the retina

In diabetic retinopathy, this loss of small blood vessels causes low oxygen delivery to parts of the retina, which then compensates by stimulating new blood vessel growth. It is the growth of these new vessels that causes intraretinal bleeding and other problems in the diabetic eye that can eventually lead to blindness.

In diabetic patients only certain cells - those that cannot prevent their internal glucose levels from rising - are damaged by hyperglycemia. Dr. Brownlee and his team discovered that a consequence of high glucose inside a cell is the overproduction of the free radical superoxide. This overproduction causes an increase in the glucose-derived molecule MG, which then turns on the angiopoietin-2 gene by directly attaching to an inhibitor of this gene and disabling it, thus resulting in blood vessel damage. The group's findings suggest that drugs which result in the suppression of MG and related molecules in cells may be of benefit in the prevention and treatment of the retinopathy. In addition, such drugs might also lead to cancer- fighting agents due to the fact that they are able to stem the growth of blood vessels, which feed tumors and may also make tumor cells more susceptible to destruction by chemotherapy.

"Based on our findings, we now believe that by reducing MG levels through yet-to-be discovered new drugs, we would normalize damaging patterns of gene expression in complication-prone diabetic cells," said Dr. Brownlee. "Control of changes in the concentration of MG also has implications beyond the realm of retinopathy, since abnormal MG metabolism has been linked to kidney failure, cancer and malaria. As such, this discovery has widespread and important implications, and we're very excited to see where this research will lead."

According to Antony Horton, JDRF's Program Director for Diabetes Complications, "Methylglyoxal is clearly an important, yet under-examined, molecule that is implicated in the disease process of two major diabetic complications: retinopathy and renal failure. We anticipate that diabetes researchers will now be able to use this information towards the development of therapies that will impact the lives of millions of people with diabetes."

Source: Diabetes In Control: