Overview

Nearly 40 million people face blindness worldwide, including more than 1 million in the U.S. While effective treatments exist in many cases, some diseases that cause blindness, such as glaucoma, have no known cure.

Glaucoma accounts for about 10 percent of all blindness. Glaucoma is generally associated with raised pressure within the eye, called intraocular pressure, which damages the optic nerve. While the risk and prevalence of glaucoma increases with age, one form of the disease—pediatric glaucoma—can strike children within the first year of life.

Simon John, Ph.D., is working to identify the genetic influences on glaucoma risk and to find new targets for more effective treatment. Other research projects at the Laboratory include investigations into the genetic influences on glaucoma risk and finding more effective treatments as well as identifying effective model systems for a variety of other eye diseases.

Research

Professor Simon John, Ph.D., working with collaborators, identified a malfunctioning gene in a mouse strain that develops both cataracts and glaucoma. The gene fails to produce an essential protein, disrupting the development of the mouse eye lens. The mice developed high intraocular pressure and optic nerve damage—the hallmarks of glaucoma—as well as cataracts.

The new findings imply that mice and patients with these mutations may not have adequate protection from oxidative stress in the drainage structures of the eye. With increasing age, their tissues may be more susceptible to oxidative damage resulting in high intraocular pressure and glaucoma.

Although further experiments are needed to be certain, this work is the first to suggest that oxidative stress response is relevant to glaucoma. John notes, "There is a growing body of literature indicating that if you disturb oxygen levels in the eye—including after cataract surgery—the risk of developing glaucoma increases."

Detecting and targeting early disease processes

John and his team have also demonstrated a groundbreaking approach to analyzing genomic data from mice that typically develop glaucoma. Using this new analysis, which "clusters" relevant data from special computer chips called microarrays, the researchers identified many molecular changes that occur very early, before detectable damage occurs.

Two of these changes—in molecular pathways known respectively as the complement cascade and endothelin system—have been associated with later stages of glaucoma in human patients. The researchers separately blocked each of those pathways and found that the mice were protected from glaucoma-related damage. The results are among the most potent neuroprotective treatments documented.