As we get older, a lot of things stop working as well as they used to. For many people, this includes their eyes getting drier, whether because they don’t produce enough tears or because their tears evaporate too fast. In severe cases of dry eye disease, people are in a lot of pain and can have trouble keeping their eyes open for any period of time, which severely impacts their day-to-day activities.
Most researchers working on dry eye disease are investigating treatments, whether eye drops or devices. Dr. William Ngo is taking a more fundamental approach – he’s working to understand cellular aging at the front of the eye.
Ngo, an assistant professor at the University of Waterloo School of Optometry and Vision Science, recently won a prestigious Discovery Grant from the Natural Sciences and Engineering Research Council of Canada (NSERC). This grant will support his research into the aging of the ocular surface over the next five years.
“Aging is the biggest risk factor for dry eye,” says Ngo. “If we understand aging, we could potentially understand how to prevent dry eye.”
Over the next several years, Ngo aims to gain a better understanding of how aging occurs in the cornea, conjunctiva and meibomian glands, as well as how the front of the eye ages in different populations and under different conditions.
A related stream of work is investigating how aging is linked to the inflammatory response in the eye. Ngo is examining gene regulation at the front of the eye, with the aim of discovering how genes are turned on and off as we get older, and how that influences inflammation.
“When you have inflammation at the front of the eye, it creates tissue damage, and tissue damage creates more dryness and inflammation, so it’s a vicious cycle,” says Ngo.
Ngo is also using bioinformatics techniques with the aim of finding novel compounds that might modulate aging and inflammation at the eye surface.
His master’s student, Cassandra Huynh, recently presented a paper at the American Academy of Optometry’s annual conference about her work using network discovery, a bioinformatics tool, to discover flavonoids that could bind to inflammatory proteins.
She did this by cross-referencing a list of inflammatory proteins associated with dry eye disease with a database that maps drug-protein interactions. She focused on flavonoids – plant-derived compounds – to find ones that can inhibit inflammatory proteins.
“You’d probably have to eat a ton of spinach to benefit your eyes, but we could potentially take these flavonoids and turn them into an eyedrop that would have much more impact,” says Ngo. “It really speeds up the discovery process when you can combine computational and wet lab techniques.”
Ngo is also supervising a PhD student, Nijani Nagaarudkumaran, who is studying cellular aging, particularly looking at autophagy, a process whereby cells break down damaged or useless proteins and reuse components.
“We know that this process of breaking down and recycling becomes impaired with age, so you have a buildup of useless junk inside a cell,” says Ngo. “Nijani is modelling this process within corneal cells and studying how the impaired cells respond to inflammatory stimuli.”
Ultimately, Ngo hopes a better understanding of the cellular aging process will lead to the discovery of a compound that can modulate aging of the ocular surface and thus prevent dry eye disease. These insights could potentially be applied to other parts of the eye or even body, he says.
“A lot of processes are shared, biologically speaking, so maybe this work will branch into other things. If we understand how aging works, we can prevent a lot of chronic diseases.”
Dr. William Ngo with two students, to his left is Shahana Vimalanathan, who is a 5th year biomedical sciences student completing her honours thesis, and PhD student Nijani Nagaarudkumaran to his right.