The exact mechanisms by which hyperglycemia causes the blood vessel damage and abnormal vascular growth in the retina and other organs of patients with diabetes is unclear. However, recent research has provided enough clues to launch animal studies and some clinical trials of agents to prevent retinopathy independent of glucose control. There are at least 4 clinical trials now testing the ability of aminoguanidine to prevent kidney and other complications from diabetes. At Columbia University's College of Physicians and Surgeons, New York, assistant professor Anne Marie Schmidt, MD, and colleagues are studying how AGEs interact with cells in hopes of finding agents to inhibit their activity. Studies have shown that interaction of AGE with RAGE results in an environment that disturbs cellular properties and enhances permeability of vessels and inflammatory cell dysfunction.
RAGE is a protein that is linked to the surface of cells by a transmembrane component.
An agent that safely and effectively blocks AGE may provide a therapy against a wide range of diabetic complications, she said. Most important, these improvements are seen in the absence of improved blood glucose levels or cholesterol and lipid profile, which suggests a unique mechanism is at work. Bursell is director of Eye Research and King, section head of Vascular Cell Biology, both at Joslin Diabetes Center, in Boston. According to the researchers, this finding suggests that it may be possible to develop an oral pharmacological agent that prevents the macular edema of diabetic retinopathy by inhibiting PKC activity. The treatment code was just broken, and the data are still being analyzed, he said.