The Jackson Laboratory Release: Researchers Substantially Lessen Glaucoma by Detecting and Targeting Early Disease Processes

March 8, 2011 Bar Harbor, Maine – Jackson Laboratory researchers and their collaborators report they have designed an analysis technique that detects early stages of glaucoma in mice, and have successfully blocked the disease by targeting some of the molecular events in those early stages.

Glaucoma, a leading cause of blindness, affects more than 4 million Americans, at least half of whom don’t even know they have the disease. Though the best-known symptom of glaucoma is elevated pressure inside the eye, blindness-inducing damage to retinal ganglion cells and the optic nerve can occur in patients with normal intraocular eye pressure. Earlier detection and treatment could therefore have a powerful impact on preventing blindness due to glaucoma.

The research team, led by Simon W. M. John, Ph.D., Jackson Laboratory professor and Howard Hughes Medical Institute Investigator, reporting in the Journal of Clinical Investigation, 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.

"These very robust protective effects," says lead author Gareth Howell, Ph.D., "pharmacologically targeting these two pathways may be effective as new treatments for human glaucoma." Human glaucoma typically progresses very slowly over the course of decades, providing ample opportunity to intervene at the early stages when these pathways are first induced.

The researchers note that Bosentan, the drug they used to block the endothelin system, is already FDA-approved to treat pulmonary hypertension and chronic heart failure. Also, although in this study they used a genetic approach to block the complement system, there are also FDA-approved complement inhibitors that are prescribed for arthritis, cardiovascular disease and other conditions.

According to Dr. Howell, the data discussed in the paper barely scratches the surface of all the molecular events that the team's cluster-based analysis revealed are altered in glaucoma-prone mice. They will make their findings available to the worldwide scientific community through a new database that they developed for this purpose.

The John lab collaborated with researchers at the University of Rochester Medical Center, the University of North Texas Health Science Center, Children’s Hospital in Boston and Stanford University School of Medicine.

This work was funded in part by the National Eye Institute, The Barbara and Joseph Cohen Foundation, the American Health Assistance Foundation and a Research to Prevent Blindness Career Development Award.

The Jackson Laboratory is a nonprofit biomedical research institution based in Bar Harbor, Maine. Its mission is to discover the genetic basis for preventing, treating and curing human diseases, and to enable research and education for the global biomedical community.

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