A self-described nomad who grew up in Malaysia, Singapore, and the US, Frederick Sebastian is fulfilling what he sees as his purpose at Northeastern, where he is completing his PhD in Bioengineering with a focus in biomechanics. A graduate of Arizona State University, where he received his undergraduate and master’s degrees in biomedical engineering, Sebastian traveled across the country to spend a year as a researcher at Dartmouth College before making his way to Boston, his ultimate destination. “The city has always had a special place in my heart. I knew this was where I was going to do my PhD, so it was only a matter of time.”
Driven by a desire to work on translational medical research where the results of his work could be directly applicable to human health, Sebastian knew that to achieve his vision he would need to act both as a research scientist and an engineer. This, in turn, led him to Northeastern, where he was attracted to the college’s support of collaboration with outside companies, as well as its network of connections to the medical technology industry in Boston.
Since 2020 he has worked and studied under Professor Rouzbeh Amini in the Laboratory for Soft Tissue Biomechanics, where his research focuses on studying the internal structures of the human eye to better understand how they relate to the progression of glaucoma. The stakes are high indeed – research suggests that by 2040 there will be at least 112 million affected by glaucoma globally, with a significant number of them going on to lose their eyesight.
While the root causes of this disease are still being studied, the two most common variants are known as Primary Open Angle Glaucoma (POAG), and Primary Angle Closure Glaucoma (PACG). In both variants a buildup of aqueous humor, the liquid filling the eye’s internal chambers, causes internal pressure on the fragile optic nerve tissue, inflicting irreversible damage and eventually leading to permanent blindness.
Sebastian’s work focuses on the PACG variant, the form of glaucoma that carries a higher burden of morbidity. The root cause of PACG is known to be changes in the shape of the iris; situated in between the cornea and lens and surrounded by aqueous humor, the iris can begin to curve inwards, creating pressure on the path through which the aqueous humor exits the interior of the eye, ultimately creating a blockage. While the “how” of PACG is known, the “why” remains a mystery, and is what occupies much of Sebastian’s time now.
“Preliminary studies have shown that the iris gets stiff in PACG patients,” Sebastian explains, “We know that some tissues stiffen over time, but we have never tested this on the eye. To put this into perspective, we don’t know anything about the internal structures of the human eye because we have never studied them. Nobody has studied the stiffness of the iris in a traditional sense before.”
He continues, “I’m currently working towards transitioning away from animal models to using irides from human cadavers. Then we can test the physical parameters of these tissues, which nobody has ever done. Nobody has ever studied the tissue in human eyes by stretching it out, scraping its surface, finding out what it takes to damage it.”
While they work towards that objective, Sebastian and his lab mates are simulating the behavior of human eye tissue through a combination of high-resolution cross-sectional photos of patients’ living eyes and a technique known as finite element mesh, or FEM, wherein an image of a three-dimensional object is overlayed with a mesh of triangles, allowing them to track in minute detail any changes to the structure of the meshed object.
By mapping the irides of both healthy individuals and PACG patients using this technique and then feeding the FEM data into a computer model, Sebastian can compare the two and see exactly how glaucoma sufferers’ eyes differ as the irides stiffen. This in turn allows them to use their computer model to simulate those changes as they would occur within the eye, allowing them to see how a healthy eye would physically change under the effects of PACG. “We want to make sure the simulation will eventually match the image we have,” he says of this technique, “Once it does, we can start to estimate the parameters of what it takes to get there.”
These are all moves in a very long game, as he sees it. “If we study the mechanics of the iris, we could potentially diagnose glaucoma based on the stiffness of the iris in future,” says Sebastian, “and it opens room for a conversation about glaucoma treatment. Current treatment for glaucoma involves using lasers to open holes in the eye for the aqueous humor to drain out – and it doesn’t always work! The success rate has been as low as 24%, with people coming back to have more holes lasered in. What if instead you could someday just take a drug that reverses the stiffness in the iris assuming we knew it causes your glaucoma?”
With plans to continue working in biotech once he graduates, Sebastian hopes to remain in the Boston area. “My goal is to do research that goes from the benchtop to the bedside as efficiently as we can make it happen,” he says, “I want to be both the scientist and the engineer, to understand both the product and the conception of it.”
