Protecting the Eye From Pressure

Blocking the activity of a single enzyme can nearly halt the nerve damage caused by glaucoma in mice, according to a paper in the current issue of the Proceedings of the National Academy of Sciences. The finding may lead to a new treatment for glaucoma, which causes more than 10,000 people in the United States alone to go blind every year.

Roughly 2% of people over age 35 have chronic glaucoma, in which fluid builds up inside the eyeball, leading to increased pressure and eventual death of cells in the optic nerve. The condition often goes undetected until the nerves are damaged. The only working treatments so far (and they often give only partial relief) are drugs or surgery that either help drain the excess fluid or slow down its production. Arthur Neufeld and his colleagues at Washington University in St. Louis are among the labs looking for ways to block the nerve damage caused by the pressure buildup. Neufeld's group recently found that the enzyme nitric oxide synthase 2 (NOS-2), which produces toxic levels of the gas nitric oxide, is active in the eyes of rats that have their eyes' drainage channels blocked, causing an artificial form of glaucoma.

To see whether NOS-2 might be causing the nerve damage, the researchers added an NOS-2 inhibitor called aminoguanidine to the rats' drinking water. After 6 months, they found that less than 10% of the animals' ganglion nerve cells had died, compared to 36% in an untreated control group. The treatment also prevented the eye region near the optic nerve from becoming cupped, as it does when the nerve is damaged.

The study impressed Paul Kaufman, an ocular pharmacologist at the University of Wisconsin, Madison. It shows that "this pathway matters in [glaucoma] and that you can actually do something about it," he says. Neufeld says he's looking forward to testing NOS-2 inhibitors in clinical trials for human glaucoma, and says that several pharmaceutical companies said they are interested in developing more specific and effective inhibitory molecules. That only adds to the growing interest in NOS-2 inhibitors, he says: The molecule is also believed to play a role in several neurodegenerative afflictions, such as multiple sclerosis and Parkinson's disease.