Diabetes-related vision loss most often is blamed on blood vessel damage in and around the retina, but new research suggests that much of that vision loss may result from nerve cell injury that occurs long before any blood vessels are damaged.
The findings could lead to new approaches to treating diabetes-related vision loss, called diabetic retinopathy, since many current treatments are aimed at damaged blood vessels.
“Many of my colleagues believe if you catch diabetic retinopathy early enough, it can be controlled with drugs that combat damage to blood vessels,” says Rithwick Rajagopal, an ophthalmologist at Washington University in St. Louis and first author of a new study published in the journal Diabetes.
“But those drugs have side effects, and the drugs are very expensive. In addition, our findings suggest there is an underlying, progressive neurodegeneration not being addressed by those therapies.”
The obesity epidemic has sparked a diabetes epidemic. Some 30 million people in the United States have some form of diabetes. As the number of people with diabetes has increased, so has the number of those with diabetic retinopathy, now the most common cause of new cases of blindness worldwide in adults ages 20-74.
For the study, researchers fed mice a high-fat diet to induce diabetes and, eventually, diabetic retinopathy. When researchers tested animals after two and then three months, they couldn’t find any problems in the mice’s eyes.
But after three months on the high-fat diet, the animals had developed obesity-related glucose intolerance, and by six months, they had nerve problems in the retina. There was no evidence of blood vessel damage in the eyes, however, until the animals were examined at 12 months.
“Interestingly, the disease came on so slowly that we were able to identify different stages of the disease,” Rajagopal says. “We found that they developed functional problems in the retina from nerve cell defects much earlier than they developed the vascular disease we normally associate with mouse and human retinopathy.”
Although current treatments for diabetic retinopathy help many people, the benefit might be greater if patients received therapies earlier in the course of the disease, particularly treatments focused on treating nerve damage, says coauthor Clay Semenkovich, professor of endocrinology, metabolism & lipid research and professor of cell biology and physiology.
“There is evidence from other studies that people with diabetes go through a phase that seems to correspond to the early nerve injury we found in the retinas of these mice. But that has been largely overlooked by many in the field because the dogma has it that diabetic retinopathy is a disease of the blood vessels.”
The most profound implication of the study is that injury to nerve tissue in the retina may occur much earlier than damage to blood vessels in the eye, Semenkovich says.
“Now we have an animal model that may help us develop therapies that address nerve damage that appears to occur long before blood vessel damage begins.”
The National Institute of Diabetes and Digestive and Kidney Diseases and the National Eye Institute of the National Institutes of Health funded the work.