Potential New Glaucoma Therapy

Glaucoma Blindness Blocker Studied By Blocking Nitric Oxide in Eyes, Researchers Hope to Slow or Prevent Blindness By LAURAN NEERGAARD

The Associated Press WASHINGTON (Aug. 16)- Scientists peering deep into the eyes of rats have discovered a new target for treating glaucoma: Blocking a chemical called nitric oxide may slow, if not prevent, the blindness. So far, it has worked only in rats. But the research is so promising that the Missouri scientists are talking with pharmaceutical companies about trying to create a drug glaucoma patients could one day use. The discovery is ''a completely different way of treating the disease,'' explained lead researcher Arthur Neufeld, an ophthalmology professor at Washington University School of Medicine in St. Louis. The work ''will likely be considered classic in years to come,'' University of Wisconsin ophthalmologist Paul Kaufman declared in reviewing their search, published in this week's Proceedings of the National Academy of Sciences. Glaucoma is the second leading cause of irreversible vision loss in the United States, and the most common cause among black Americans. An estimated 3 million Americans have glaucoma, and 120,000 are blind as a result. In glaucoma, pressure inside the eyeball increases to high levels because eye fluid doesn't drain properly. Eventually, that pressure damages the optic nerve and progressively eats away vision. Until now, all treatment has been aimed at easing that pressure, either with medicated eye drops or surgery. But ''even with very effective lowering, there are a significant number of people who continue to lose vision,'' said Dr. Carl Kupfer, director of the National Eye Institute. ''The exciting thing about ... (the new discovery) is that it represents an entirely new and different way'' of fighting glaucoma. Neufeld knew other scientists had discovered that excessive levels of a body chemical called nitric oxide can be toxic to certain tissues. What if nitric oxide, he wondered, also was toxic to eye tissue? That question led off a chain of discoveries. First, Neufeld examined human eye tissue from glaucoma patients, and discovered an enzyme called NOS-2 that makes excessive - destructive - amounts of nitric oxide. ''I knew that nitric oxide must be at very high levels'' in patients' eyes, Neufeld said. But did it cause the glaucoma, or was it merely a byproduct of dying cells in the retina? So Neufeld turned to an animal model of glaucoma, clogging up rats' eyes until their optic pressure built enough to begin destroying their sight. Sure enough, their eyes harbored NOS-2, also. Neufeld never treated the pressure in any of the rats' eyes. Instead, he put into some of the rats' drinking water an experimental drug called aminoguanidine that can inhibit NOS-2. Six months later, the rats who didn't drink any medicine had lost 36percent of their retinal cells - but the medicated rats had lost less than 10percent of those crucial vision cells, even though their eye pressure had never been lowered. ''By blocking the nitric oxide, we protected the optic nerve,'' Neufeld explained. That suggests both that nitric oxide buildup is a cause of glaucoma, and that lowering the chemical might prove an important treatment. There are no nitric oxide-lowering drugs sold today, Neufeld cautioned, and it will take at least five years to test experimental glaucoma drugs. Unlike the experimental medicine Neufeld fed rats, developing a nitric oxide-blocking eyedrop would be better for people, Kupfer said. That way, it could be tested in just one eye of each patient - so if potential drugs fail or prove harmful, the other eye would be untouched. Because nitric oxide is a target in other diseases, pharmaceutical companies already were hotly researching nitric oxide blockers, and Neufeld said he's already in discussions about creating a glaucoma drug.