Diabetes :: Joslin discovers protein that causes blood vessel leakage and swelling with diabetic retinopathy

Joslin researchers discover protein that causes blood vessel leakage and swelling in eyes with diabetic retinopathy. Discovery one day could lead to new treatments for eye diseases and brain swelling caused by head injury, stroke and other conditions.

Although health professionals have had success in treating diabetic retinopathy, two forms of the disease — proliferative diabetic retinopathy and diabetic macular edema — still are the leading causes of vision loss and blindness among working age adults in the developed world. Now a Joslin Diabetes Center-led team of investigators has compiled the most complete inventory yet available of the proteins present in a part of the human eye known as the vitreous and has identified a group of proteins that may play critical roles in causing blood vessel leakage in the eyes of people with this common form of diabetic eye disease.

In the new study, published in the Jan. 28 online edition of the journal Nature Medicine, lead investigator Edward Feener, Ph.D., and his team also found that one of these molecules causes the leakage of retinal blood vessels, which contributes to the retinal swelling (diabetic macular edema or DME) that is often associated with advanced diabetic retinopathy. These findings suggest potential new therapeutic targets for the treatment of diabetic retinopathy and DME and also could provide new opportunities for treating cerebral swelling caused by head injury, stroke and other conditions.

“By analyzing the protein composition in the human vitreous (the gel fluid that fills the cavity of the eye between the lens and the retina), we have identified a new group of molecules that may improve our understanding of the disease processes that contribute to diabetic retinopathy. By studying the actions of these proteins in both the retina and the brain, we have shown that our findings may have broad relevance for neurovascular leakage and swelling,” said Dr. Feener, Investigator in Joslin’s Section on Vascular Cell Biology, Director of Joslin’s Proteomics Core, which hosted the study, and Assistant Professor of Medicine at Harvard Medical School.

The work was funded by grants from the Juvenile Diabetes Research Foundation (JDRF), the Massachusetts Lions Eye Research Fund, the National Institutes of Health, the Adler Foundation, and the Air Force Office of Scientific Research Medical Free Electron Laser Program.

“Millions of people worldwide live with diabetic retinopathy and the accompanying threat of severe vision loss or blindness. While some treatment is available in the late stages of this condition, the incidence of proliferative diabetic retinopathy and diabetic macular edema still pose the serious threat of sight loss. Going forward, Dr. Feener’s findings could provide new opportunities for the development of treatments for diabetes-related vision loss,” said Dr. Helen Nickerson, Scientific Program Manager for Complications at JDRF.

Diabetic retinopathy, one of the most common complications of diabetes, is characterized by a range of abnormalities that develop from the damage caused by high blood glucose levels on the small blood vessels of the retina. Proliferative diabetic retinopathy (PDR) is diagnosed when the retina begins to form new blood vessels to counteract this damage, new vessels which in turn often bleed and blur or block vision. More than 700,000 patients in the United States have PDR, and more than 63,000 patients develop it annually. Diabetic macular edema occurs as the leaky blood vessels cause the macula (the central area in the retina responsible for sharp central vision) to swell. DME affects more than 500,000 patients in the U.S., with 56,000 new cases diagnosed yearly.


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