Diabetes' Toll on Vision

Donald G. Puro Photo: Richard Hackel

Kellogg researchers edge closer to understanding the pathways of diabetic eye disease

Tiny cells called pericytes may play a pivotal role in setting off the chain of events that leads to diabetic eye disease, according to Donald G. Puro, M.D., Ph.D., professor of ophthalmology and visual sciences and of physiology in the U-M Medical School. Pericytes are tiny cells which sit on the wall of capillaries throughout the body but are most concentrated in the retina.

Diabetes takes its toll on vision by damaging blood vessels in the retina, and Puro believes pericytes could be involved in the flow of blood in the retina. Diabetes affects some 16 million Americans, many of whom don’t realize they have the disease. About two-thirds of the patients Puro sees in Kellogg’s General Ophthalmology Clinic suffer from diabetes.

Using a technique developed by Puro’s team to isolate capillaries from the retina, the researchers study the functions of pericytes under controlled laboratory conditions. After viewing the isolated vessels with time-lapse photography, members of the team observed an intriguing phenomenon: the pericytes contract, and this action may change the flow of the blood. According to Puro, “It’s reasonable to ask whether pericytes are part of a control mechanism that is essential to blood flow in the retina. Perhaps diabetes causes the pericytes to malfunction, and this is the first action in a cascading series of events leading to vision loss.”

For some reason the eye’s capillaries are extremely vulnerable to the elevated glucose that accompanies diabetes. “It’s the Holy Grail,” says Puro. “If we can prove which feature makes the eye so vulnerable, presumably we could modify it.”

Puro notes that Kellogg has the only research team studying capillaries with the patch-clamp technique, in which fine-tipped glass tubes form a seal with the surface of a pericyte. The method essentially allows researchers to “listen in” on vital aspects of cellular activity. Says Puro, “We think pericytes respond to all sorts of signals about how to control blood flow in the retina.”

In a related series of experiments, the Kellogg research lab is collecting more clues to describe the chain of events and the pathways in diabetic eye disease. This line of research reveals that pericytes operate as a community rather than simply as individual units. Puro and his coworkers recently discovered that this communication between cells within retinal capillaries is severely disrupted soon after the onset of diabetes, bringing the research team a step closer to understanding how diabetes affects vision: it may disrupt the ability of capillaries to supply essential oxygen and nutrients to the nerve cells of the retina.

“We are still trying to better understand what is ‘normal behavior,’” Puro says, “so that we can intervene when the cells begin the abnormal behavior associated with diabetes. If we can understand the process early on, we could almost certainly prevent damage down the road.”

—BN