Looking Beyond Pressure-Lowering Drugs to Treat Glaucoma

Glaucoma is known to damage neurons that extend from the retina to the brain and are critical for producing sight. Specifically, the disease affects the long fibers, or axons, of nerve cells (neurons) known as retinal ganglion cells at the head of the optic nerve. But the exact link between the mechanics of the optic nerve head and the degeneration of these axons in glaucoma remains poorly understood.

Shruti Patil, PhD, a BrightFocus Foundation National Glaucoma Research grant recipient, hopes to solve the mysteries of retinal ganglion cell axon degeneration—and obtain insights that could inspire new therapies for glaucoma. Her grant project is focused on developing an innovative 3D model that simulates the movement and structure of the optic nerve head, a gateway for signals traveling from the retina to the brain. She aims to use the model to study how glaucoma changes the optic nerve head and how that affects the health of retinal ganglion cell axons.

“I want my research to improve the lives of people who I may never meet, but knowing that my work would help them in some way,” she said.

Beyond Pressure-Lowering Drugs

Treatment innovations, like Dr. Patil’s study, are a part of BrightFocus Foundation’s 360-degree approach, which examines glaucoma from multiple angles. This is important in glaucoma, where the standard of care is regulating intraocular pressure. Many models used to study the degeneration of the eye in glaucoma involve elevating pressure to simulate damage from the disease.

By designing a model that focuses more on the environment and mechanical properties of the optic nerve, Dr. Patil, a postdoctoral researcher at Indiana University School of Medicine, could uncover discoveries that lead to therapeutic interventions beyond pressure-lowering drugs.

Dr. Patil’s model focuses on the region of the optic nerve head. This region includes a mesh-like tissue that supports the nerve fibers as they leave the eye. In glaucoma, this tissue can become stiffer than normal, possibly damaging the axons of retinal ganglion cells.

To create the 3D model of this region of the optic nerve, Dr. Patil’s team is using human stem cells and materials called hydrogels, which are soft, water-rich substances similar to Jell-O, she explained.

“What makes them powerful for our research is that we can finely adjust, or ‘tune’ how stiff they are. This lets us create controlled environments that mimic the healthy or diseased conditions of the optic nerve head,” she said. “Once this model is validated, I plan to use it as a tool to study how progressive stiffening of the tissue microenvironment contributes to axonal degeneration.”

From Cancer to Eye Disease

Dr. Patil’s interest in science was sparked by her father, a clinical biochemist in Mumbai. With his encouragement, she pursued her fascination with how cells are composed and how they interact with other cells, initially studying cancer biology.

In the early part of her research career, Dr. Patil focused on identifying novel chemotherapeutic strategies in a type of brain tumor called medulloblastoma. While pursuing a master’s degree and then a PhD in cancer biology at the University of North Texas Health Science Center, she met researchers from the North Texas Eye Research Institute.

“Their work on glaucoma fascinated me, not only because of the clinical relevance and complexity of the disease, but also because of the strong translational potential to help preserve vision and quality of life for millions,” Dr. Patil said. She decided to pivot to glaucoma research.

“Though the path from cancer to glaucoma may seem like a leap, it’s felt like a natural evolution for me, driven by curiosity, strong mentorship, and the desire to make meaningful contributions to understanding complex diseases,” she said.

During her PhD and post-doctoral training, Dr. Patil has used innovative approaches to model glaucoma biology and explore novel treatment approaches. She is now training with Jason Meyer, PhD, associate professor of medical and molecular genetics at Indiana University School of Medicine and a member of the Stark Neurosciences Research Institute. Dr. Meyer, also a National Glaucoma Research grantee, led a team that used a human stem-cell model to discover a genetic mutation linked to vision damage in glaucoma. In a landmark 2016 study, his team created and treated retinal ganglion cells derived from the skin cells of people with glaucoma for the first time.

Mimicking Stiffness to Study Cell Damage

For her current study, Dr. Patil plans to create the 3D model by embedding human stem cell-derived retinal ganglion cells and astrocytes—a type of brain cell that supports the function of neurons—into hydrogels. Her team will alter the stiffness of the gels so they can study how different stiffness levels affect the health and behavior of the cells, focusing on the survival and structure of retinal ganglion cell axons.

Isolating stiffness as a key feature in glaucoma development and progression “helps us take an important first step toward untangling the biomechanical side of glaucoma, which could eventually lead to new therapeutic strategies,” Dr. Patil said.

In the long term, Dr. Patil plans to use the 3D model to delve more deeply into increased stiffness of the tissues supporting nerve cells in the eye and how they induce dysfunction in retinal ganglion cells and surrounding cells. Ultimately, the model could become a testing platform to evaluate potential drugs or therapeutic interventions aimed at mitigating stressors in the eye that contribute to glaucoma progression.

Transformational Support

Dr. Patil said that being a BrightFocus Foundation National Glaucoma Research recipient has allowed her to pursue her research passions while being mentored by leaders like Dr. Meyer. She has also participated in several BrightFocus Foundation workshops for early-career scientists, including Glaucoma Fast Track and biennial symposia.

“The support from BrightFocus Foundation has been transformational for both my professional development and the direction of my research,” she said. “I’ve connected with other fellows and established investigators, which has not only inspired new ideas but also provided valuable feedback on my work.”

“This level of engagement fosters a sense of community that strengthens the field and accelerates progress toward new treatments and diagnostics,” she added.

Your support can help drive the next generation of glaucoma breakthroughs. BrightFocus Foundation’s National Glaucoma Research program empowers scientists like Dr. Patil to explore bold, early-stage ideas that could lead to entirely new treatment pathways. Explore how you can help advance innovative vision research.