Discovery of a new mechanism that can lead to blindness

An important scientific breakthrough by a team of researchers led by Michel Cayouette, PhD, of the IRCM and Université de Montréal, is being published today by The Journal of Neuroscience. The Montreal scientists discovered that a protein found in the retina plays an essential role in the function and survival of light-sensing cells that are required for vision. These findings could have a significant impact on our understanding of retinal degenerative diseases that cause blindness.

The researchers studied a process called compartmentalization, which establishes and maintains different compartments within a cell, each containing a specific set of proteins. This process is crucial for neurons (nerve cells) to function properly.

“Compartments within a cell are much like different parts of a car,” explains Vasanth Ramamurthy, PhD, first author of the study. “In the same way that gas must be in the fuel tank in order to power the car's engine, proteins need to be in a specific compartment to properly exercise their functions.”

A good example of compartmentalization is observed in a specialized type of light-sensing neurons found in the retina, the photoreceptors, which are made up of different compartments containing specific proteins essential for vision.

“We wanted to understand how compartmentalization is achieved within photoreceptor cells,” says Dr. Cayouette, Director of the Cellular Neurobiology research unit at the IRCM. “Our work identified a new mechanism that explains this process. More specifically, we found that a protein called Numb functions like a traffic controller to direct proteins to the appropriate compartments.”

“We demonstrated that in the absence of Numb, photoreceptors are unable to send a molecule essential for vision to the correct compartment, which causes the cells to progressively degenerate and ultimately die,” adds Dr. Ramamurthy, who carried out the project in Dr. Cayouette's laboratory in collaboration with Christine Jolicoeur, research assistant. “This is important because the death of photoreceptor cells is known to cause retinal degenerative diseases in humans that lead to blindness. Our work therefore provides a new piece of the puzzle to help us better understand how and why the cells die.”

“We believe our results could eventually have a substantial impact on the development of treatments for retinal degenerative diseases, like retinitis pigmentosa and Leber's congenital amaurosis, by providing novel drug targets to prevent photoreceptor degeneration,” concludes Dr. Cayouette.

According to the Foundation Fighting Blindness Canada, millions of people in North America live with varying degrees of irreversible vision loss because they have an untreatable, degenerative eye disorder that affects the retina. Research aiming to better understand what causes vision loss could lead to preserving and restoring sight.

About the research project

This research project was funded by grants from the Canadian Institutes of Health Research, the Foundation Fighting Blindness Canada and the Fonds de recherche du Québec – Santé. The project was conducted at the IRCM by Vasanth Ramamurthy, Christine Jolicoeur, Demetra Koutroumbas and Michel Cayouette, in collaboration with researchers in the United States and Germany.

For more information, please refer to the article summary published online by The Journal of Neuroscience: www.jneurosci.org/content/34/42/13976.short.

About Michel Cayouette

Michel Cayouette obtained a PhD in neurobiology from Université Laval. He is Associate IRCM Research Professor and Director of the Cellular Neurobiology research unit. Dr. Cayouette is an Associate Research Professor in the Department of Medicine at Université de Montréal. He is also Adjunct Professor in the Department of Medicine (Division of Experimental Medicine) and in the Department of Anatomy and Cell Biology at McGill University. He is Chair of the Scientific Advisory Board for the Foundation Fighting Blindness Canada, as well as a member of the Vision Research Network (Fonds de recherche du Québec – Santé) and the Centre of Excellence in Neuroscience of Université de Montréal. Dr. Cayouette is a Senior Research Scholar from the Fonds de recherche du Québec – Santé. For more information, visit www.ircm.qc.ca/cayouette.

About the IRCM

The IRCM (www.ircm.qc.ca) is a renowned biomedical research institute located in the heart of Montréal's university district. Founded in 1967, it is currently comprised of 35 research units and four specialized research clinics (cholesterol, cystic fibrosis, diabetes and obesity, hypertension). The IRCM is affiliated with the Université de Montréal, and the IRCM Clinic is associated to the Centre hospitalier de l'Université de Montréal (CHUM). It also maintains a long-standing association with McGill University. The IRCM is funded by the Quebec ministry of Economy, Innovation and Export Trade (Ministère de l'Économie, de l'Innovation et des Exportations).

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For more information and to schedule an interview with Dr. Cayouette, please contact:

Julie Langelier

Communications Officer (IRCM)

julie.langelier@ircm.qc.ca

(514) 987-5555

Lucette Thériault

Communications Director (IRCM)

lucette.theriault@ircm.qc.ca

(514) 987-5535