Dark side of a blood builder: hormone linked to diabetic blindness.

Since 1989, physicians have prescribed the hormone erythropoietin (EPO) to combat anemia from blood loss, kidney failure, and cancer treatments. This compound orchestrates red blood cell production. But researchers in Japan now report that EPO may damage a person's vision.

The scientists found unusually high concentrations of EPO in the eyes of patients with advanced diabetic retinopathy, the leading cause of blindness among nonelderly adults in the industrialized world. In the Aug. 25 New England Journal of Medicine (NEJM), the researchers suggest that suppressing EPO might alleviate this type of retinopathy. They acknowledge, however, that doing so might not be easy.

In individuals with retinopathy, certain eye problems or the high blood sugar concentrations of diabetes lead to bleeding from tiny vessels feeding the light-sensing retina. There can also be leakage of the thick vitreous fluid that fills the eyeball. Either of these conditions can set in motion a chain reaction that builds up scar tissue and, over years, creates new, weak blood vessels that leak and obscure vision.

The team in Japan analyzed vitreous fluid drawn from 73 patients with retinopathy who had diabetes--for 12 years, on average--and from 71 others whose retinopathy stemmed from other eye diseases. The researchers discovered that study volunteers with diabetes had 12 times as much EPO in the eye fluid as the other patients had.

In lab tests, the fluid from patients with diabetic retinopathy stimulated the growth of retinal blood vessel cells from cows. When the scientists added a compound that neutralizes EPO, the cell growth in the lab dishes slowed, says study coauthor Hitoshi Takagi, an ophthalmologist at Amagasaki Hospital.

Previously, scientists had identified a protein, vascular endothelial growth factor (VEGF), in the eyes of people with diabetic retinopathy. Tests in mice show that VEGF and EPO independently trigger the growth of leaky blood vessels, Takagi says.

The new data "provide strong evidence to suggest that EPO is another important factor" in stimulating aberrant vessel growth in diabetic retinopathy, says Lloyd Paul Aiello of Harvard Medical School and the Joslin Diabetes Center in Boston in the same NEJM issue. Takagi and his colleagues suggest that high blood sugar or other stresses boost EPO production in the eye.

Doctors currently use lasers to remove abnormal accumulations of vitreous fluid and aberrant blood vessels growing in the retina. Such treatment leaves the eye's center intact, but patients sometimes lose some peripheral and night vision.

A drug called pegaptanib, which is already on the market, counters VEGF in another eye condition. Both VEGF and EPO may provide targets for drug treatment of diabetic retinopathy, says Takagi.

A drug that suppresses EPO might have drawbacks, notes George L. King, also of the Joslin Diabetes Center and Harvard Medical School. He cautions, for example, that diabetes patients often need EPO to counter anemia from kidney problems.

Takagi suggests that administering an anti-EPO agent directly to the eye might avoid such problems.