Glaucoma is one of the leading causes of blindness worldwide, affecting millions of people and often progressing silently until vision loss becomes irreversible. Cutting-edge research from a University of Wisconsin vision scientist is exploring a groundbreaking approach that could change how we treat this disease—by addressing its root cause with gene therapy.
Glaucoma typically occurs when the optic nerve, the nerve at the back of the eye that transmits signals to the brain, is damaged, most often from high eye pressure (intraocular pressure). This high pressure occurs when the fluid (aqueous humor)in the eye either builds up from a blockage or overproduction, or from other medical conditions and injuries. In its early stages, glaucoma often presents no noticeable symptoms, such as pain or vision changes, making early detection difficult.
While glaucoma cannot be cured, current treatments can slow its progression by lowering eye pressure. These include daily eye drops and, in some cases, surgery. However, many patients—especially children and older adults—struggle to stick with this demanding regimen, leading to poor outcomes.
There’s a critical need for therapies that are easier to manage and more effective. That’s where Dr. Gillian McLellan, a professor in the Department of Ophthalmology and Visual Sciences, comes in.
“Unlike traditional treatments that focus on managing symptoms, we are exploring a strategy that aims to provide long-lasting relief from a single treatment,” said Dr. McLellan. “It targets the biological changes that lead to glaucoma, offering hope for a more effective and sustainable solution.”
The project, on which Dr. McLellan serves as principal investigator, received $440,000 in funding over two years from the National Institutes of Health.
At the heart of this research is a protein called TGFβ2, which is found in high levels in the eyes of people with glaucoma. TGFβ2 contributes to the stiffening of a part of the eye called the trabecular meshwork—a drainage system that helps regulate eye pressure. When this meshwork becomes rigid, fluid builds up, increasing pressure inside the eye and damaging the optic nerve.
To tackle this, Dr. McLellan and her team are using a cutting-edge technique called CRISPR interference. Unlike traditional CRISPR, which cuts DNA to edit genes, this method uses a modified version that blocks harmful gene activity without altering the DNA itself. Think of it as turning down the volume on a gene that’s too loud.
“In earlier studies completed by my collaborator at Indiana University, this approach successfully reduced TGFβ2 levels in lab-grown human eye cells and lowered eye pressure in mice,” Dr. McLellan explained. “Now, we are taking the next step: testing the therapy in cats that naturally develop early-onset glaucoma due to a genetic mutation. Cats closely mimic the human condition, making them ideal for studying potential treatments.”
The project involves two key phases. First, scientists will fine-tune the delivery system—using a virus that’s harmless to cats—to ensure the therapy reaches the right cells in the eye safely and effectively. Then, they’ll design a set of genetic “blockers” to target both TGFβ2 and its receptor, TGFβR1, and test their ability to reduce eye pressure and prevent optic nerve damage.
If successful, this research could pave the way for a new kind of gene therapy that works regardless of a patient’s specific genetic makeup.
“This research is a promising step toward a future where glaucoma can be treated not just managed,” Dr. McLellan said, “and where vision loss might one day be a thing of the past.”