Understanding the Causes of Glaucoma

Although glaucoma affects more than 400,000 Canadians, scientists still don’t really understand how this disease causes vision loss. We know that glaucoma permanently damages the retinal ganglion cells, critical nerve cells that carry images from the light detecting parts of the retina to the visual centers of the brain. Current glaucoma treatments work to reduce pressure in the eye, which reduces the risk of glaucoma, but doesn’t directly address the damage to vision cells.
Signals sent by glial cells can help protect the eye from glaucoma.

To understand glaucoma and the process of cell injury caused by increase eye pressure, Jeremy Sivak and his colleague, John Flanagan, study the stresses in the eye that occur when a person shows early signs of glaucoma. Their work has come to focus on glial cells. These nerve cells surround the crucial retinal ganglion cells that enable vision, normally providing support and nutrients. Increasingly Donald K Johnson Eye Institute researchers are demonstrating that glial cells are important partners in vision – guiding the growth and development of vision cells and either helping protect them from damage, or in many cases, helping to cause damage as part of a local inflammatory cascade.  Dr. Sivak has recently demonstrated for the first time that this inflammatory switch in retinal glial cells can be targeted therapeutically to protect retinal ganglion cells from damage.

By analysing these signals and developing complex computer models of cell communications, Drs. Sivak and Flanagan have begun to identify signals that make cells more vulnerable to mechanical injury and to develop strategies to help protect vision. One outcome from their work concerns a molecule called PEA-15, which is produced when cells are stretched by increased pressure. Changes in PEA-15 levels trigger an inflammatory switch in glial cells leading to the death of retinal ganglion cells and causing extensive vision loss. In parallel, Dr. Sivak has also identified signals produced due to other relevant stresses, such as lack of oxygen and nutrients in the retina due to compromised blood flow. Learning to understand these signals and developing drugs to control them, could help protect the eyes of people with early signs of glaucoma from further damage.

This research is support by grants from the Canadian Institute of Health Research and the Glaucoma Research Society of Canada.