Searching for a solution to blindness

When most people consider how vision works, they think of light and optics and how nerves transmit that information to the brain. What is often forgotten is that those nerves—like any other cell in the body—need a supply of blood to function. When diseases like diabetes threaten to cut off blood supply to the retina, the adaptive overgrowth of the microvessels with deprived nutrition places a person’s sight at risk.

The rods and cones inside the retina—layers of cells at the back of the eyeball—sense light and send signals to the brain to yield instantaneous images of objects and landscapes. These retinal cells consume more oxygen per tissue mass than most other cells in the body, so a complex network of tiny blood vessels support their metabolic needs.

“Failure of these microscopic blood vessels to perform their functions may lead to blindness and a profound loss of contact with the outside world,” said Lih Kuo, PhD, professor and vice chair of the Department of Medical Physiology at the Texas A&M College of Medicine. “If the vessels have a problem and the nerves cannot get the nutrients and oxygen that they need, the cells will degenerate and die, causing blindness.”

Nearly 30 million Americans have been diagnosed with diabetes, and a major complication of diabetes and high blood sugar is damage to the retina called diabetic retinopathy, which causes abnormal blood vessels (with the potential to bleed) to grow while also causing normal blood vessels (capillaries) to close, often leading to vision loss.

The blood vessel damage can happen very quickly.

“The striking thing is that in animal models, after only two weeks of increased sugar in the blood, we can see the functional impairment in the eyes,” said Kuo, who is also the director of the Ophthalmic Vascular Research Program (OVRP), a basic science/clinical partnership between the Departments of Medical Physiology at Texas A&M and Ophthalmology at Scott & White Medical Center in Temple, Texas. “The initial damage can lead to long-term impairment that is irreversible.”

Kuo’s background is in the study of isolated microscopic blood vessels of the heart to understand the coronary microcirculation. When he began to study the microvessels of the eye, he realized that although the blood vessels were about the same size—smaller than a human hair—they did not behave at all the same way. “We see differences between the coronary system and the eyes,” Kuo said. “After two weeks of high blood sugar, we see damage to both, but the mechanism is not the same. Antioxidants, for example, seem to help blood vessels in the heart, but not in the eye in our initial observations. Interestingly, high sugar activates different enzymes to cause functional damage of microvessels in the heart versus in the eyes.” The OVRP is committed to the development of tissue-specific drug delivery and therapy, which is the goal of translational research.

“If you study the heart, the information you get may not necessarily be extrapolated to the eye, and vice versa,” Kuo said. “We need to be careful when obtaining information from one system, because it may or may not be applicable to the other. Even when a drug does the same thing in both, the underlying mechanism may be different.”

Still, some of the same preventive measures that are part of a healthy lifestyle—good diet, exercise and control of blood sugar and blood pressure—benefit both the heart and the eye. “The eye is just one of the organs,” Kuo said. “What is good for the rest of the body is also good for the eyes, but each organ has an independent environment.”

Until recently, these separate environments had not been well studied, and the techniques of studying the coronary circulation had not been applied to the tiny vessels of the eye. “The eye is overlooked,” Kuo said. “It’s difficult to study, because the vessels are so small and not readily accessible.”

The OVRP team sought to fill the gap. “We hope to discover how the blood vessels in the eye work and how abnormal function of these vessels impacts various eye diseases,” Kuo said. “The ultimate goal is to save people’s vision.”

Kuo and his research team (Travis Hein, PhD, professor of surgery, and Robert Rosa, MD, professor of surgery and medical physiology) are one of the only labs in the world able to isolate the tiny blood vessels while they are alive. “Other labs isolate the microvessels, but the tissue is not viable and the vessels do not develop basal tone on their own,” Kuo said. “In order to characterize the behavior of diseased vessels, it is essential to understand the activity and reactivity of viable and healthy vessels as a baseline for proper comparison.”

The function of the microvessels is important because they control the blood flow. Just like the individual faucets in each home control the flow of water through the water pipe distribution system, the microvessels and their constriction or dilation control the tissue blood flow in the body.

“Using a simple clinical instrument, we can actually watch the blood circulate in the eyes,” Kuo said. “The eyes really are a window to your health.”