Some of the biggest leaps researchers at the Alan S. Crandall Center for Glaucoma Innovation are taking come in small packages. Scientists are vetting new surgical devices so small they require a microscope to view. They are building molecules for the center’s first glaucoma drug. And they are studying how exosomes—the smallest portion of all nanoparticles released by human cells—might be used to treat or detect glaucoma.
The Crandall Center at the John A. Moran Eye Center fosters success in the science of small by encouraging large, interdisciplinary teams to share disease models and test new ways of treating glaucoma together. Researchers and physicians alike are looking toward a future when they can use a simple blood test to diagnose glaucoma and provide treatments that prevent vision loss.
“When you’re doing this kind of science, it really does take a village,” says Crandall Center Associate Director David Krizaj, PhD. “We are recruiting highly accomplished glaucoma researchers from across the country to turbocharge our output, and we are funding new research paradigms. All the puzzle pieces that need to come together for that future are assembled at the University of Utah.”
A NEW DRUG
Krizaj has spent the better part of his career tunneling deep into a narrow topic.
Glaucoma is not a well-understood disease, and it has taken Krizaj more than a decade to understand exactly how a muscular tissue in the eye known as the trabecular meshwork senses and regulates the eye’s internal fluid pressure. This mechanism is key to understanding glaucoma, a potentially blinding disease characterized by high fluid pressure. This elevated pressure kills the cells that make up the eye’s optic nerve, which is responsible for sending information from our eyes to our brain to create vision.
Now, Krizaj is using his knowledge to develop a potential new therapy, a one-two punch that stands to be the Crandall Center’s first blockbuster medication. Lab tests have shown his approach successfully lowers pressure; however, the jaw-dropping novelty of the treatment is its potential ability to also prevent optic nerve cells from dying —a function known as neuroprotection.
There are no neuroprotective drugs on the market for glaucoma, and one that could deliver such treatment would revolutionize care.
While universities have traditionally looked to big pharma to translate their discoveries into drugs, Moran has been changing that paradigm. Its Sharon Eccles Steele Center for Translational Medicine (SCTM) establishes partnerships among philanthropists, industry, and academic scientists to speed up drug development. Krizaj points to the SCTM model when describing how interdisciplinary collaboration and private funding will take his discovery from bench to bedside.
Krizaj needed the help of other researchers—chemists and pharmacologists—and private investor funding to complete his work. The research team includes scientists at the University of Utah who are experts in synthetic and medicinal chemistry, organic and bioorganic chemistry, and pharmacology and toxicology.
“Different fields have different priorities, standards, and expectations,” says Krizaj. “That means you have to learn and respect where other people are coming from and then negotiate to find common ground. You have to merge visions of what a successful treatment is.”
The team is in the final stretch of experiments using disease models and next will apply to the FDA for permission to begin testing in humans.
Until the past decade, glaucoma patients had the choice of taking several costly prescription eye drops daily for life or undergoing invasive surgeries with high complication rates and long recovery times.
Championed by Crandall Center Director and world-renowned surgeon Iqbal “Ike” K. Ahmed, MD, FRCSC, micro-invasive glaucoma surgery (MIGS) changed all of that. MIGS places microscopic devices smaller than 1 mm inside the eye to drain fluid and lower pressure, and it is becoming the cornerstone of modern glaucoma care. Ahmed leads the field in designing and testing new MIGS devices.
Among the devices he’s studying at the Crandall Center are a new laser for glaucoma surgery and an adjustable MIGS device that can be customized for each patient.
So-called “cold,” or excimer, lasers generate power from light in the ultraviolet range, and ophthalmologists already use them for procedures such as LASIK. Now, glaucoma surgeons might use the ELIOS excimer laser to create microscopic openings in the trabecular meshwork.
These holes would allow more fluid to drain out of the eye, reducing pressure.
“Currently, we use instruments and devices to remove parts of the drainage channel in a rudimentary way,” explains Ahmed. “An excimer laser is a more precise way to do that with less tissue damage. So much of glaucoma surgery is based on how the eye heals, so anything that can reduce the amount of tissue trauma is potentially better for patients.”
Ahmed is also testing a unique new MIGS device by Myra Vision. The device allows a surgeon to adjust fluid outflow at any point after surgery.
“One of the problems we have with glaucoma devices is that they are set with just a standard flow for all patients, and for some that might be too low, for others too high,” explains Ahmed. “This implant allows us to use a laser to open or close valves to determine how much flow we want at any given time for any given patient. This allows us to really customize the amount of drainage we have to each patient to reach the right target pressure.”
Born in Ireland, Fiona McDonnell, PhD, joined the Crandall Center in 2022 by way of Duke Eye Center.
She specializes in one of the most exciting new areas of glaucoma research—nanoparticles released by all cells in the human body called exosomes. They have several potential applications in new therapies or diagnostic tests.
Studying exosomes, which are 20-150 nanometers in size, requires specialized expertise and equipment—not to mention patience, as she must painstakingly separate them from other cells. Funded by the National Eye Institute, McDonnell is trying to find exosomes specific to the trabecular meshwork—something that could one day help develop a simple blood test for glaucoma. She will also study whether introducing healthy exosomes to damaged cells can repair them.
“If so, a new treatment might be as easy as taking exosomes from a healthy donor or from another part of the body that is not diseased and introducing them into the eye,” explains McDonnell. “It’s similar to stem cell therapy in that you’re using the patient’s own cells.”
Exosomes are already used as carriers to introduce drugs into other parts of the human body. Now, McDonnell wants to see if they can deliver glaucoma therapies to the back of the eye.
SCTM Executive Director Gregory S. Hageman, PhD, has changed the world’s understanding of age-related macular degeneration (AMD), a blinding disease impacting adults 55 and over. He and his team clarified the genetics and pathology of the disease. Now he’s testing his team’s first therapy in humans.
Hageman has noticed a potential connection between AMD and glaucoma. Genetic variants on chromosome 1 that increase a person’s risk for developing AMD also appear to increase a person’s risk for developing glaucoma. He’ll explore the finding as head of the Crandall Center’s Translational Research Initiative.
“While the SCTM approach was first used to study AMD, we are now excited to focus on glaucoma,” says Hageman. “There is so much work to do, and we have an amazing team of experts to do it.”