Identification of Pivotal Molecules that Regulate the Loss of Nerve Cells in Glaucoma

Leonard A Levin, MD, PhD
Board of Regents of the University of Wisconsin System, School of Medicine and Public Health (Madison, WI, United States)
Year Awarded:
2012
Grant Duration:
July 1, 2012 to June 30, 2014
Disease:
Glaucoma
Award Amount:
$100,000
Grant Reference ID:
G2012015
Award Type:
Standard
Award Region:
US Midwestern

Redox Sulfhydryl Modifications as a Glaucoma Biomarker

Summary

The irreversible loss of vision in glaucoma is caused by damage to the optic nerve and the death of nerve cells, but the details of how the damage causes the death is still not known. Dr. Levin and colleagues believe that there are one or more pivotal signals that are critical to this pathway, based on how they can be blocked by new drugs called phosphine-borane complexes. Identifying these pivotal signals could help with early detection of glaucoma, before it causes significant visual loss; could help in monitoring the response to therapy; and even help to design new and better therapies for the disease.

Details

Dr. Levin and colleagues are trying to pin down exactly how the eye gets disconnected from the brain in glaucoma, with the goal of preventing the disconnection from happening.

Fortunately, the researchers have some clues as to what is going on. Levin and colleagues have tested unique drugs that block the disconnection process. It turns out that those drugs work by separating molecules that were abnormally linked together. If the molecules are unlinked, then the eye stays connected to the brain, and vision is preserved.

But that's not the whole story. The problem is that the abnormally linked molecules have not yet been identified. The researchers plan to use sophisticated techniques to identify those molecules, check that they are indeed abnormally linked together in glaucoma, and confirm that the new drugs separate the links and maintain the connection of the eye to the brain.

This project is novel because it focuses on the abnormal linkage of a key molecule as being critical for disconnecting the eye from the brain in glaucoma. It also will help in further developing newer and innovative unlinking drugs, which might someday become useful treatments for glaucoma. If the project is successful, and depending on the identity and accessibility of the abnormally linked molecules, these results may lead to ways of detecting glaucoma at its earliest stages. A test for an increase in these abnormally linked molecules may also help to tell whether a patient is getting worse, so that new interventions can be attempted before their vision is lost.

About the Researcher

Leonard A. Levin, MD, Ph.D., FARVO, is Professor of Ophthalmology and Visual Sciences at the University of Wisconsin and Canada Research Chair in Ophthalmology and Visual Sciences at the University of Montreal. His research program focuses on mechanisms of retinal ganglion cell death at the molecular, tissue culture, and whole animal level. This includes the role axonal damage plays in inducing loss of retinal ganglion cells and how axons themselves undergo injury, an area common to ophthalmology and neurology. He is particularly interested in using advanced imaging techniques to study signaling of cell death in the retina and the development of new drugs for optic nerve and retinal disease, particularly glaucoma.