As the number of diabetes cases rises in the United States, so does the incidence of diabetic retinopathy, a potentially devastating eye disorder that often afflicts long-term diabetics.

If caught early, diabetic retinopathy can be treated successfully. But often, there are no early warning signs; and the disease can lead to blindness. For these reasons, early diagnosis and treatment are critical.

Robert Linsenmeier, Ph.D., of Northwestern University -- who received a Biomedical Engineering Research Grant in 1985 -- is among the biomedical engineers who are contributing to our understanding of diabetic retinopathy, opening the door to more effective treatments.

Part of his work deals with the transfer of oxygen from the bloodstream to retinal tissue. The retina is unusual in that it has two separate blood supplies. The first is called the retinal circulation, a network of arterioles, capillaries and venules that infiltrate the tissue, but only supply about half of the retinal thickness. The second supply comes from a sheet of capillaries that originate in an adjacent region, the choroid. These capillaries supply the retina by diffusion of substances across the boundary between the retina and the choroid.

In one line of investigation, Linsenmeier and a multidisciplinary group of collaborators discovered that in diabetic retinopathy, oxygen deprivation occurs at a much earlier stage of the disease than had been realized.

A crippling feature of the disorder occurs when capillaries release fluid and lipids onto the macula, the central part of the retina that enables us to see details. The macula swells and vision blurs. As the disease progresses, new, fragile blood vessels form that can rupture and bleed into the retina. This can also blur vision and lead to retinal destruction.

By the time these blood vessel impairments occur, the retina is not getting all the oxygen it needs. But has oxygen deprivation occurred earlier in the disease and, if so, how might this affect vision?

To investigate this question, Linsenmeier and his colleagues used microelectrodes to record oxygen levels in areas of the central retina of diabetic animals. They made sure to avoid visible blood vessels so the readings would come from the tissue itself. Similar readings were made from disease-free animals.

Two subsequent analyses were performed. In the first, the oxygen readings were applied to a model of retinal oxygen diffusion and consumption to determine how much oxygen was being used by the light-sensitive photoreceptors. In the second analysis, an average was taken over the half of the retina supplied by the retinal circulation to determine mean oxygen levels.

The researchers found that animals with long-standing diabetes had about half as much oxygen in the inner half of their retinas as did healthy animals. Some of the diabetic animals had almost no oxygen in the inner retina, but other areas of their retinas appeared normal. These observations were made in animals with a few micro-aneurysms, an early manifestation of the disease, but with a circulation that appeared normal otherwise.

"This is the first direct demonstration of reduced retinal tissue [oxygenation] at any stage of retinopathy," the researches wrote in Investigative Ophthalmology & Visual Science. This finding has implications for the diagnosis and treatment of diabetic retinopathy.

Many blinding diseases -- including retinopathy of prematurity, vascular occlusive disease, and some types of glaucoma -- originate in the vascular system.

One of the first problems to result from vascular defects is that eye cells and tissues do not get the oxygen they need, a condition called hypoxia. Deprived of oxygen, cells begin to break down.

In diabetic retinopathy, medical scientists have speculated that hypoxia stimulates fluid leakage and vessel proliferation. Some researchers believe these consequences might be avoided by preventing early hypoxia. Linsenmeier and his group are also investigating other retinal diseases in which vascular or genetic problems cause abnormal retinal metabolism.

By combining microelectrode measurements with mathematical models of diffusion, they have gained insight into problems as diverse as retinal detachment, retinitis pigmentosa, and branch retinal artery occlusion.

Using similar techniques they plan to investigate the rationale for one of the main treatments for diabetic retinopathy, panretinal photocoagulation, in which laser surgery is used to coagulate leakage from the tiny vessels of the retina. A side effect is the destruction of retinal tissue. The goal of their investigation is to optimize the treatment and spare more of the retina.

The rate of type 2 diabetes rose by 9 percent annually between 1987 and 1996, according to the San Antonio Heart Study. Diabetes afflicts nearly 16 million Americans, causing complications that include blindness, kidney disease, heart disease and amputations. It is the sixth leading cause of death in this country.