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The Fundamentals: Eyes and Ears

Often overlooked as part of the brain, these portals of perception are essential to living to our full potential

Our eyes and ears absorb information from all directions, converting it into signals that enable us to experience images and sound, and act accordingly. We are often unaware of this process until something goes wrong, owing to injury or issues that accrue with age or disease. Herein, a glimpse at what three investigators in the Brain Sciences Research Program at Sunnybrook Research Institute (SRI) are doing in the field.

Dr. Peter Kertes

Ophthalmologist and scientist Dr. Peter Kertes is using ocular imaging to try and develop a novel test for early diagnosis of Alzheimer’s disease.

Photo: Curtis Lantinga

Windows to the Brain

As scientists uncover more about the link between the brain and the health of the blood vessels that nourish it, being able to study the vasculature of the eye noninvasively presents opportunities to learn more about development of brain diseases.

“The retina is essentially externalized brain,” says Dr. Peter Kertes, a researcher and chief of ophthalmology at Sunnybrook Health Sciences Centre. “We have a real advantage insofar as the retina is the only place where you can look at blood vessels directly just by looking into the eye.”

His research focuses on diseases of the retina, the light-sensitive tissue at the back of the inner eye, which functions like camera film to record an image of what we are seeing before sending it to the brain for processing.

Kertes, who is also a professor at the University of Toronto, was among the first in Canada to evaluate a drug called ranibizumab to treat diabetic macular edema, a complication of diabetes that leads to vision loss and affects about 60,000 Canadians. Retinal blood vessels leak fluid, which causes swelling in the macula, a part of the retina responsible for sharp vision. This swelling causes impaired vision.

Ranibizumab works by blocking vascular endothelial growth factor, a molecule that promotes growth of new blood vessels and vessel “leakiness.”

Kertes and his group at Sunnybrook were part of an international clinical trial that showed the drug was superior to laser therapy, which reduces swelling by welding leaky vessels shut. Laser therapy prevents further impairment but rarely improves vision, says Kertes, who notes this and other research on ranibizumab has influenced clinical practice and health policy. In 2008, Ontario approved coverage of the drug for people aged 65 years and older.

“Now we use ranibizumab. When somebody presents with diabetic macular edema, they can expect an improvement in their vision. Patients will gain an average of two ‘lines’ of vision [in an eye test], which is a big difference from laser,” says Kertes.

He’s also peering at the blood vessels of the retina for clues about development of Alzheimer’s disease (AD), for which there is no single diagnostic test. He’s teamed up with Dr. Sandra Black, director of the Brain Sciences Research Program at SRI and a cognitive neurologist, to look at the relationship between retinal blood vessel diameter and AD.

The study involves 35 of Black’s patients with a clinical diagnosis of AD. The pair are using measurements of retinal vessel diameter and correlating this with other neuroimaging data that show structural and pathological changes in the brains of these patients, as well as results of cognitive testing.

The research is in early stages, but Kertes says he is excited at the prospect of using ocular imaging to gain insight into how AD begins. “It gives us the potential to diagnose problems noninvasively. As treatments come online, it allows patients to be treated earlier and more successfully.”

Drs. Vincent Lin and Alain Dabdoub

Drs. Vincent Lin (left) and Alain Dabdoub are searching for biological solutions for hearing loss, a condition that affects three million Canadians.

Photo: Curtis Lantinga

What Was That?

Biological scientist Dr. Alain Dabdoub is uncovering the developmental processes unfolding in a less accessible sense organ: the ear. Dabdoub directs the Sonja N. Koerner Hearing Regeneration Laboratory at SRI, where he and his colleagues are working toward biological solutions for hearing loss. It is the only lab in Canada doing such research.

Hearing impairment, estimated to affect about 3 million Canadians, results from loss of hair cells, which translate sound vibrations into electrical signals; and auditory nerve cells, which transmit these signals to the brain. Birds and other non-mammals can regenerate these cells spontaneously. We are not so lucky; once lost—to disease, noise or injury—they are gone for good.

Dabdoub is studying how these cells form in development for leads on how they can be restored. “We are learning how these neurons develop and what genes we can use to regenerate them,” says Dabdoub, who is also an assistant professor at U of T.

He has shown he can grow these cells in vitro by injecting a gene to induce the formation of hair cells and auditory neurons. “The great thing about the cochlea is you can harvest it at embryonic stages, before any of these cells have developed, and you can manipulate them in your incubator as time goes by. Within a week you can have a nice organ formed,” says Dabdoub.

He is zeroing in on the Wnt signalling pathway, which is important in ear development because it regulates the division and differentiation of cells. Dabdoub is trying to identify which of the Wnt family of proteins are responsible for signalling in the cochlea, which could serve as targets for drugs and gene therapy.

Their goal is to develop therapies that will cause the organ to restore itself.

Dr. Vincent Lin, a clinician-scientist at SRI who specializes in hearing regeneration, collaborates with Dabdoub. They are analyzing differences in how the Wnt pathway is modulated in embryonic versus adult tissue, specifically, changes in Wnt signalling molecules. “Studying inner ear development provides important insights into regeneration, which in many ways is like development recapitulated in an older animal. As we do more analysis of cochlear tissue from many age ranges, from embryonic to adult, we’re going to identify more molecules of interest,” says Lin, who is an otolaryngologist and cochlear implant surgeon at Sunnybrook, and an assistant professor at U of T.

Their work has been mainly in cell culture, but they are moving their experiments to preclinical models that mimic the human hearing system. As they learn more about the mechanisms that trigger regeneration of the cells that enable hearing, their goal is to develop therapies that will cause the organ to restore itself to a functional, natural state.

Are we close?

Lin is cautiously optimistic. “We’re only a few breakthroughs away from moving forward with that. Those could happen tomorrow, or they could take years. Science doesn’t work in a linear fashion; there are often big jumps. When it happens is anybody’s guess.”

Dabdoub’s research is supported by the Canada Foundation for Innovation, National Institutes of Health, and Ontario Ministry of Research and Innovation. Kertes’ research is supported by the Canadian Retina Foundation, Physicians’ Services Incorporated Foundation and industry. The study to validate an eye test to help early detection of dementia is led by Dr. Sandra Black, and funded by Brain Canada and the W. Garfield Weston Foundation. Lin’s research is supported by the Canadian Institutes of Health Research, Hearing Foundation of Canada and industry.

Dr. Peter Kertes
Drs. Vincent Lin and Alain Dabdoub