Harnessing the Power of Zebrafish to Fight Blindness: An Interview with Dr. Sarah McFarlane

October 1st, 2018 by FFB Canada

Question: Hi Dr. McFarlane! Can you please introduce yourself and tell us how you became interested in vision research and zebrafish?

Dr. McFarlane: I am a Professor in the Department of Cell Biology and Anatomy at the Hotchkiss Brain Institute at the University of Calgary. For more than 25 years, I have been privileged to work in the world of discovery science, where scientists try to identify the fundamental mechanisms that drive biological processes such as vision. I really enjoy figuring out how things work and getting students interested in the natural and biological world around them. I still get excited when I look through the microscope!

This fascination was developed as a postdoctoral researcher at the University of California, San Diego, where I was introduced to the beauty of the eye, as well as the devastation that occurs when eye cells stop working properly and vision fails.

I firmly believe that understanding the eye is absolutely necessary if we are going to achieve our shared, long-term goal of developing effective sight-saving treatments. We need to understand how different cells in the eye are made and how they behave so that we can remake them in a culture dish and use them to replace or sustain injured retinal cells.

We now use the zebrafish as our model. The eyes of these fish are formed in a manner very similar to how a human eye is made, and we have generated tools that allow us to follow the development of a specific type of cell, called retinal pigment epithelium (RPE) cells, in real time, which is obviously not possible in humans or other mammals. Knowing how RPE cells behave and move normally in zebrafish will hopefully give us extra control of their movements when developing new sight-saving treatments for human beings.

Question: Can you please explain how your FFB-funded research project is helping us to fight blindness?

Dr. McFarlane: Age related macular degeneration (AMD) involves the degeneration of cells of the retinal pigment epithelium (RPE), a key tissue that provides critical support for the light sensing cells called photoreceptors. Some of the cell replacement therapies for AMD are aiming to transplant new, healthy RPE cells to replace damaged ones; to be successful, these transplanted RPE cells will have to migrate to the sites of RPE damage. In our work we are studying zebrafish to learn more about  how RPE cells move normally, and the key molecules that promote and direct those movements. We hope that this new knowledge can be used to help ensure the successful development of cell replacement therapies for AMD.

Question: We know that funding vision research is essential to driving the development of new sight-saving treatments. Can you explain how your research is contributing to the creation of new therapies?

Dr. McFarlane: Ultimately, our team hopes that our research will contribute to the development of many different successful therapies; this is because any researcher who is trying to understand the molecules that promote the survival, differentiation, and movements of RPE cells in retinal diseases can use the new knowledge that we’ve created! Thanks to funding from the FFB, we’ve described the behaviours of the early (naïve) cells, how they then go on to become RPE cells, how they move, and what molecular signals drive these movements. Based on this information, we have engineered tools that allow us to track RPE cells in live zebrafish, and to also track their response in the adult to injury or to the degeneration of photoreceptors.

Question: One of the most common questions that we receive from our community is: how long before there are treatments for my eye disease? How would you answer this question?

Dr. McFarlane: My laboratory is focused on a kind of research called “discovery research” – in this kind of “early stage” research, our aim is to define the molecular and cellular processes that underlie a particular biology. In our case, we are trying to learn more about how the cells of the retina are formed, move, and function. We need this basic information to understand what goes wrong in retinal diseases, and the best strategies to create treatments that have the potential to correct the defects. Without this information, there is a risk that experimental treatments will not be successful at the clinical trial stage.

Moreover, this basic information will generally help guide and inform research that will eventually be translated to the treatment of retinal disease. While discovery research is absolutely essential for us to understand and treat retinal disease, it is very challenging to develop a firm timeline to show when and how basic science discoveries will help the community of vision researchers and create successful new treatments.

Question: In your opinion, what is the most important thing that patients affected by blinding eye diseases can do to help accelerate research progress?

Dr. McFarlane: I think it’s very important for the entire FFB community to ask the Federal Government to increase funding support to government science funding agencies, such as the Canadian Institutes of Health Research (CIHR) and the Natural Science and Engineering Research Council (NSERC). These funding agencies are the primary funders of health science and discovery research in Canada. Increasing this funding would accelerate the production of the fundamental knowledge that is needed to ensure that new and effective sight-saving treatments can be developed in the future.

Because there is such a great need for more vision research funding, patients and families who are living with blinding eye diseases can also help to accelerate the development of new treatments by making a donation to the Foundation Fighting Blindness!

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