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There's a saying that the eyes are the gateway to the soul, and work being done at the Krembil Research Institute is finding that the eye, specifically the retina and how it reacts to light, is indeed a signpost for more bodily conditions.
For many years, the retina's rods and cones were said to be responsible for vision, with rods working at low light levels and delivering limited colours, and cones being active under brighter light, allowing for the perception of thousands of colours. Known as photoreceptors, rods and cones contain chemicals that change when hit with light. About 15 years ago, a third class of photoreceptors was discovered. Called intrinsically photosensitive retinal ganglion cells (ipRGCs), these long-unrecognized tiny cells are proving to be big players in conditions such as sleep disturbance, as well as in pain levels. At Krembil, an ophthalmologist is shining light on the significance of ipRGCs that go beyond seeing what's around us.
"The amazing thing about these photoreceptors is that they are crucial for some biological phenomena," says Dr. Agnes Wong, a Senior Scientist at Krembil and a physician at The Hospital for Sick Children and a professor in the Department of Ophthalmology and Vision Sciences at the University of Toronto. "They control the sleep-wake cycle, and they are primarily responsible for controlling pupil function."
Aware of how colour affected ipRGCs, Dr. Wong and her team conducted an experiment in 2014, in which 10 subjects were exposed to blue light and red light to determine how their ipRGCs responded. The use of coloured light and its effect on pupil size and reaction is known as chromatic pupillometry and the reaction is called postillumination pupil response (PIPR).
Dr. Wong's team found that brighter blue light caused increasingly greater PIPR on ipRGCs, while red light induced no PIPR.
Using her first-hand knowledge of how blue light affects the ipRGCs, Dr. Wong is exploring the prevalent condition of light sensitivity. "Photophobia (painful sensitiveness to strong light) is a very common symptom of many eye diseases and neurological diseases," she says. Eye inflammation, migraine and postconcussion effects are conditions that can cause photophobia, which is poorly understood and difficult to treat.
Dr. Shaobo Lei, an ophthalmologist working as a research fellow with Dr. Wong, notes that ipRGCs work like light meters and send pain messages along nerve pathways. "When light levels reach a certain level, they signal to pain pathways. It's why patients have (photophobia) painful, unpleasant experiences with bright lights," he says.
One dilemma is that the pain experienced is subjective, so knowing exactly how much pain a person feels is hard to determine. "There's no good way to assess or confirm levels," says Dr. Lei, who has worked with Dr. Wong since 2012.
The doctors are now looking for a way to determine when pain starts by using chromatic pupillometry to measure the pupil's reaction to light and how it is mediated by ipRGCs. "We can measure the threshold of light intensity that causes pain," Dr. Lei says. "We can calculate or estimate at what level of light intensity that pain starts. But it's different in every person. It's different in photophobia patients, compared to a person without photophobia."
The team has narrowed its focus somewhat, setting its sights on migraine patients, who typically experience painful headaches and disturbed vision. The doctors are trying to determine if those who experience migraines are more sensitive to blue light-activated ipRGCs. If they are, one solution for those who experience migraines may be to wear glasses that block or filter blue light, Dr. Wong says.
The two doctors are also interested in why blue light induces more tears than red light. "There's a big difference between red light and blue light. It's consistent with features of ipRGCs," Dr. Lei says.
Also of interest to Dr. Wong and Dr. Lei are Alzheimer's patients, some of whom experience sleep disorders that could be related to how they react to light, or the lack of it, and by extension, their circadian rhythms.
Research has found that a subset of Alzheimer's patients has lost or have diseased ipRGCs, Dr. Wong says. It remains unknown what causes the demise of the photoreceptors. "The next question is, 'Can we monitor the progress of Alzheimer's by measuring ipRGCs? Is it a natural progression?'" says Dr. Wong.
Since earning her MD degree at Montreal's McGill University in 1994, followed by her PhD in neuroscience at the University of Toronto, Dr. Wong has found that "the more we discover, the more questions we have."
But as a rare breed of doctor with the title of clinician-scientist, she views herself as a bridge. "As a scientist, I speak one language. As a clinician, I speak another. I consider myself a translator. I see clinical questions from the practical side. I do lab research, get answers and return to the patient with the answers."
Her development of the chromatic pupillometry technique is allowing her to collect invaluable information about the little-understood pathways of ipRGCs and the possibly significant implications for patients.
This content was produced by The Globe and Mail's Globe Edge Content Studio, in consultation with an advertiser. The Globe's editorial department was not involved in its creation.