New Research Sheds Light on Mechanisms of Glaucoma
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NEW RESEARCH SHEDS LIGHT ON MECHANISMS OF GLAUCOMA
WASHINGTON, DC December 7, 2006 - New research in a mouse model of glaucoma clarifies a new mechanism by which increased pressure in the eye leads to the wasting away of cells in the retina and optic nerve and, ultimately, to vision loss. The findings, published in the December 6 issue of The Journal of Neuroscience, point to novel potential treatments for the neurodegenerative disorder, which affects nearly 70 million people worldwide.
Lead author Toru Nakazawa, MD, PhD, and researchers at the Massachusetts Eye and Ear Infirmary, Children's Hospital Boston, and Harvard Medical School demonstrated a role for the inflammatory molecule tumor necrosis factor-alpha (TNF-alpha) in the progression of glaucoma. Previous studies had suggested such a link might exist.
"The findings are conclusive," says Leonard A. Levin, MD, PhD, of the department of ophthalmology at the University of Montreal. "The quality of the research showing the mechanism of disease progression is excellent."
Working with young male mice, the researchers induced elevated pressure -- the most important risk factor in glaucoma -- in one eye. Within three days, they found, TNF-alpha levels had shot up, the result of a threefold increase in TNF-alpha gene expression.
The team then linked this increase in activity to the breakdown of oligodendrocytes, cells that support and protect newly formed nerve cells in the retina. Their study showed that the number of oligodendrocytes dropped 55 percent within two weeks. Destruction of retinal ganglion cells (RGCs), which send visual information from the eye to the brain, followed: After four weeks, more than 25 percent of RGCs had died.
Nakazawa and his colleagues suggest that the rapid rise in TNF-alpha triggers the activity of microglia, the immune defense cells of the central nervous system. Microglia attack oligodendrocytes, leaving the nerve cells in the retina exposed and vulnerable. By blocking TNF-alpha or by deleting the TNF-alpha gene or its receptor, the researchers were able to maintain original levels of the protective cells, even though intraocular pressure was high.
"Drugs that inhibit TNF-alpha, including monoclonal antibodies and soluble receptors that soak up TNF-alpha, have already been used to treat other inflammatory diseases, such as rheumatoid arthritis," says Nakazawa. Blockers to act against TNF-alpha or microglia could be developed as an alternative to current pressure-relieving glaucoma treatments, he says.
The work was supported by an award from the Alcon Research Institute, a Bausch & Lomb fellowship award, the National Eye Institute, and the National Institutes of Health.
The Journal of Neuroscience is published by the Society for Neuroscience, an organization of more than 36,500 basic scientists and clinicians who study the brain and nervous system. Senior authors Larry Benowitz, PhD, and Joan Miller, MD, can be reached at larry.benowitz@childrens.harvard.edu and Joan_Miller@meei.harvard.edu.
