Q&A: New horizons for glaucoma research

Preeminent glaucoma scientist Gulab S. Zode, PhD, recently joined the UCI School of Medicine’s Department of Ophthalmology and its Center for Translational Vision Research. His current projects are supported by several prestigious grants from the National Institutes of Health and the Alcon Research Institute. He recently shared what drew him to UCI and its vision research center.

Q. What brought you to the Department of Ophthalmology?

The quality of work coming from the department and its reputation for ocular research were highly attractive for me. The department has exciting basic and translational research programs with world-renowned faculty like Krzysztof Palczewski, PhD, and others. Also, although the department is very strong in retina research, they did not have any scientists dedicated to the particular aspect of
glaucoma that I study.

Q. What is the focus of your glaucoma research?

My research aims to understand intraocular pressure regulation and its relationship to glaucoma. Intraocular pressure, which is elevated in glaucoma patients, is created by aqueous humor dynamics. Aqueous humor is a transparent fluid that provides nutrition to eye tissues.
It gets filtered through a specialized structure known as trabecular meshwork. When a patient has glaucoma, their trabecular meshwork blocks the aqueous humor from flowing out normally, which increase pressure in the eye. Yet none of the current treatments for glaucoma target the trabecular meshwork.

My research focus is explaining why trabecular meshwork outflow is blocked in patients with glaucoma, then targeting these pathologies for treatment. In particular, we are studying how a mutation in a glaucoma gene called myocilin can cause damage to the trabecular meshwork. We have discovered that mutant myocilin is misfolded and it accumulates abnormally in trabecular meshwork cells, which results in elevated intraocular pressure and glaucoma. We are now studying cellular processes, including autophagy, which can degrade and remove the abnormal proteins from the eye and cure glaucoma.

Q. What led you to study glaucoma?

I come from a small village in India and I didn’t have a lot of choice in subjects when I first came to the United States for graduate school. As a postdoctoral student at the University of Iowa, I ended up working with a clinician who was doing ocular research. He would bring patients
to talk with us, including many people who were blind. I began to see his perspective, what motivated him — he always worked to benefit the patient. Around that time, we discovered a treatment for juvenile-onset glaucoma and I saw an opportunity to do translational research that could really help people.

Q. With more than 3 million Americans suffering from glaucoma, what potential treatments offer the most promise?

As far as our translational science, there are two exciting prospects I’m working on. One is the small molecule approach and the other is gene editing. In both, we are targeting the gene myocilin, which affects trabecular meshwork and therefore eye pressure. It is one of the known causes of inherited types of glaucoma. With the small molecule approach, we’re working on developing a chemical that can easily travel through cells to treat the myocilin and can be delivered through an eye drop. With gene editing, we would correct the mutation at cellular DNA level, which could get rid of the disease permanently for the patient. That is what also attracted me to UCI: I’m able to work directly with glaucoma clinicians to develop treatments for these patients.