The Thief of Sight
Glaucoma, often called the silent thief of sight, gradually robs patients of their peripheral vision, often without warning. Characterized by an increase in eye pressure, which may damage healthy retinal cells and the optic nerve, glaucoma can lead to blindness. Today, glaucoma affects nearly 3 million people in the US. Early detection, medication, or surgery often can control the increase in eye pressure.
Pressure Kills Healthy Cells
While studying the mechanisms that cause pressure to damage the eye, Moran researcher David Krizaj, PhD, and his team made exciting discoveries that relate cell injury in glaucoma to that from blast pressure. When the head is subject to an explosion, the eye鈥檚 cellular tissues distort and rupture due to the over-pressurized wave that envelopes the body. This causes retinal detachment, death of retinal cells, damage to the optic nerve, and vision loss. "In recent wars, massive explosives targeting people and vehicles have exposed so many soldiers to blasts鈥攊t is alarming," says David Krizaj, PhD. "As a result, eye damage among infantry has skyrocketed."
But How?
Collaborating with other departments from the University of Utah and worldwide, Krizaj鈥檚 team researched how cells communicate with each other. They knew that pressure and inflammation caused eye damage, and they knew that pressure could be reduced with medication and surgery, but they didn鈥檛 know how the eye senses pressure and how that pressure kills cells. "We thought that if we could find that mechanism, we could block those pressure sensors with pressure-reducing drugs, and we could protect cells from dying from pressure. And we did it!"
The group identified the pressure sensors in neuronal cells that die in glaucoma and found that with new drugs that target pressure-sensitive ion channels in their membranes, they could protect these cells. Importantly, they also discovered that these sensors are localized to two other types of retinal cells known to be impacted in glaucoma and by blast injury: astrocytes and microglia鈥攁moeba-looking glial immune cells. Their job is to feed neurons, remove metabolic waste, and get rid of unhealthy cells; however, if they become over activated, they start to release chemicals that can be deadly to neurons.
Confused Astrocytes and Microglia Cells
Krizaj鈥檚 team discovered that astrocytes and microglial cells get confused when strongly activated by different types of mechanical stress, such as intraocular or blast pressure, and they wreak havoc in the surrounding brain tissue. "They sense the pressure, think the healthy cell is dead and that tissue is damaged, swarm like a pack of angry wolves, release molecules meant to kill, and attack it鈥攍iterally eating our brain," says Krizaj. "That is what we want to stop. The over-active cells make blast-induced cell damage worse. But we don鈥檛 want to kill astrocytes or microglia cells; they are critical in development. Ideally, we want to control their activity鈥攌eep them quiet by controlling the stress and the excessive swelling. Because excessive swelling is the most immediate problem after the blast, we hope our new therapies will help mitigate injury by reducing pressure immediately following blast impact in the field."
Saving Sight-Saving Lives
Since finding that treatments to reduce pressure in glaucoma are relevant to treatments for traumatic blast injuries, Krizaj鈥檚 team has received a grant from the Department of Defense to develop drugs that could be administered onsite as an injection or a pill for blast-trauma patients. Their goal is to reduce immediate pressure-induced swelling and inflammation and hopefully to prevent long-term functional damage to the soldier. In the past year, Krizaj鈥檚 team has developed and patented therapies that will soon go to clinical trials.