Joslin Researchers Identify New Role for Protein in Blood Vessel Growth in Diabetic Eye Disease
BOSTON — February 27, 2002 — A recent study by researchers at Joslin Diabetes Center in Boston published in the Proceedings of the National Academy of Sciences offers further evidence that a protein called protein kinase C beta (PKC ß) is involved in the development of diabetic retinopathy, a leading cause of blindness in adults with diabetes. In a multicenter clinical trial, Joslin is testing a drug that is an inhibitor of PKC ß ?that may halt the damaging proliferation of blood vessels in the retinas of people with diabetes.
In addition, the researchers report that in their animal studies they have identified that a well-known protein, retinoblastoma protein (Rb), may be intricately involved in the PKC activation process that leads to the uncontrolled growth of blood vessels, ultimately leading to damage in eyes, kidneys and other organs in people with diabetes.
"It has been known for some time that PKC and vascular endothelial growth factor (VEGF) are important in diabetic eye disease," said George King, M.D., acting director of research at Joslin Diabetes Center and Professor of Medicine at Harvard Medical School, a lead author of the study.
"Furthermore, we have known for some time that Rb proteins have a role in regulating the growth of tumors. This is the first time Rb has been shown to have a role in blood vessel growth in the eye," Dr. King said.
The discovery of the protein action, if confirmed by further studies, could lead to new drugs to inhibit proliferation of blood vessels in the retina, he said. It also could lead to new drugs to promote angiogenesis, blood vessel growth in organs like the heart where more vessels are sometimes needed to compensate for blockages, Dr. King said.
People with diabetes are at greatly increased risk of developing a wide range of blood vessel complications, including diabetic eye disease called diabetic retinopathy, which can cause sight loss and even blindness. According to the Centers for Disease Control and Prevention, diabetic retinopathy causes 12,000 to 24,000 new cases of blindness each year in the United States.
"The study found that in animals with increased PKC activation, worse blood vessel growth occurred in their eyes, which corresponds to what happens in people who have diabetes. In animals where PKC ß activity was reduced, the animals had less blood vessel growth in the eye. This strongly suggests that inhibiting PKC ß would inhibit excessive blood vessel growth in the eye," said Lloyd Paul Aiello, M.D., Ph.D., a co-author of the study. Dr. Aiello is Assistant Director of Joslin's Beetham Eye Institute, a researcher in Vascular Cell Biology at Joslin, and an Associate Professor of Ophthalmology at Harvard Medical School. Other Joslin investigators included Kiyoshi Suzuma, M.D., Noriko Takahara, M.D., Ph.D., Izumi Suzuma, M.D., Keiji Isshiki, M.D., Ph.D., Kohjiro Ueki, M.D., Ph.D., and Michael Leitges, M.D.
Excessive growth of new blood vessels is a major cause of blindness in people with diabetes. Researchers at Joslin have shown that activation of PKC increases the blood vessel growth (or angiogenic) process and they have shown previously that PKC also is involved in vascular endothelial growth factor signaling within cells.
These findings support ongoing clinical trials headed by Dr. Aiello and being performed at Joslin and over 100 other centers throughout the world.
Researchers have known for some time that the activation of PKC ß by elevated blood sugar in people with diabetes helps trigger vascular disease. Dr. King, a pioneer in the idea of PKC being a cause of diabetes-associated complications, was instrumental in the drug's development and performed many of these studies.
Research for this latest study was supported with funding by the National Institutes of Health.
