Research Suggests New Treatment Approaches For Glaucoma

Adapted from Children’s Hospital Boston

New research from Children's Hospital Boston and the Massachusetts Eye and Ear Infirmary (MEEI) may help explain how glaucoma causes blindness, revealing the chain of events that ultimately damage the optic nerve, preventing visual information from traveling from the eye to the brain. The study, done in mice, indicates possible targets for intervention, including an inflammatory molecule called tumor necrosis factor-alpha (TNF-alpha), which is already targeted by some existing drugs.

"These findings give a whole new approach to thinking about glaucoma therapy," says Joan Miller, M.D., chief of Ophthalmology at the MEEI and a coauthor of the study, which will appear online December 6, 2006 in the Journal of Neuroscience.

Working in a mouse model, the researchers made several key observations. They showed that:

Elevated intraocular pressure causes levels of TNF-alpha to increase in the retina;
The rise in TNF-alpha activates microglia, cells that comprise part of the eye's immune system;
The activated microglia kill many of the optic nerve's oligodendrocytes (support cells that produce and maintain myelin, the insulating coating on nerve fibers);
retinal ganglion cells (RGCs), the nerve cells in the eye that send visual information to the brain via the optic nerve, subsequently die off, consistent with previous research establishing that oligodendrocyte loss leads to the death of RGCs.

"The end stage of glaucoma is a loss of retinal ganglion cells," says senior author, Dr. Larry Benowitz. "We now have good evidence that TNF-alpha plays an essential role in this loss."

"In the clinic, lowering intraocular pressure is a reliable treatment for glaucoma, but sometimes it is hard to lower the pressure even after eyedrop treatment or surgery," says lead author, Toru Nakazawa, M.D., Ph.D., now at Tohoku University in Japan. "Here we show that blocking TNF-alpha function may have a benefit as a neuroprotective treatment."

Drugs that inhibit TNF-alpha—including monoclonal antibodies and soluble receptors that soak TNF-alpha up and remove it from action—already exist and have been used to treat other inflammatory diseases such as rheumatoid arthritis, the researchers note.

"These drugs have potent systemic effects, so we'd want to develop a very safe long term and local treatment," says Miller. "Theoretically, it might be possible to put slow-release TNF alpha inhibitors just outside the eye, so you wouldn't have to have frequent injections."