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The Krizaj Lab: Glaucoma Treatment BREAKTHROUGH


Glaucoma gradually robs patients of their peripheral vision, often without warning. Increased pressure (IOP) within the eye damages healthy retinal ganglion cells (RGCs) and the optic nerve, leading to vision loss. Ideally, glaucoma treatment should combine IOP-lowering medications with treatments that protect damaged RGCs. No new glaucoma drugs have been launched over the past decade, in part because the mechanism that causes IOP to harm RGCs was unknown. David Krizaj, PhD, a vision scientist at the Moran Eye Center, and his team knew that pressure could be reduced with medication and surgery, but they didn’t know how or why pressure selectively kills RGCs, the cells that send visual signals from the retina into the brain. "So we researched how cells communicate with each other. We hypothesized that if we could identify the pressure-sensing mechanism that causes pressure to damage the eye, we could then target those cells by developing new pressure-reducing drugs," notes Krizaj. "We found it—and we were able to successfully protect cells from dying."


Krizaj’s team discovered pressure sensors in two types of retinal cells—retinal ganglion neurons and glial cells (which provide nutrients to neurons). When subjected to major stress, such as intraocular or blast pressure, over-activated glial cells wreak havoc in the surrounding retinal tissue and exacerbate cell damage caused by the trauma. "The important part is not to let these over-active cells damage the retina while preserving their normal function, which is critical in developing and adult eyes," says Krizaj. "Ideally, we want to control their activity—keep them quiet by controlling the stress and the excessive swelling, which is the most immediate problem after the blast."

A grant from the Department of Defense allowed the team to develop drugs that can be administered in the field and that will immediately mitigate blast injury to soldiers by reducing pressure. These drugs dramatically lower IOP and are highly effective in protecting RGCs from stress and neural death. The new drugs have been patented, licensed to Krizaj’s company, Asha Vision LLC (Asha means hope or bringing of the light in Sanskrit), and are currently being tested in preclinical trials with positive outcomes. The next big step will be going to clinical trials to determine the safety and efficacy in humans. The potential advantages—simultaneous control of IOP, control of inflammation, and protection of neurons—would be game-changers for the treatment of glaucoma, traumatic eye and brain injury, and epilepsy.