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Apr 5, 2016

Will You Develop Wet Age-related Macular Degeneration? Your MicroRNA May Hold The Answer

Mike Sapieha and his lab colleagues

Caption: FBC-funded scientist Dr. Mike Sapieha (7th from the left) along with his laboratory group at the Hôpital Maisonneuve Rosemont.

Will you develop the wet form of age-related macular degeneration (AMD)? Right now, doctors don’t have a way to answer this question. Thanks to a new discovery by Fighting Blindness Canada (FBC)-funded researchers, a predictive test is on the horizon.

In Canada, AMD is the leading cause of blindness in people over the age of fifty. There are two forms of AMD: dry and wet. Typically, AMD first develops as the dry form of the disease. About 10% of people living with dry AMD will eventually develop wet AMD—this is when the majority of vision loss happens. To stave off disease progression, doctors recommend taking vitamins (AREDS formula), wearing sunglasses, and eating healthy foods for your eyes. Regrettably, even the most diligent followers of these doctor’s orders may still develop wet AMD.

Fortunately, there are very effective anti-VEGF treatments for wet-AMD (such as Eylea, Lucentis, and Avastin), which are administered regularly by an injection into the eye. For most people, these treatments work wonders at preventing further vision loss and have even been shown to restore some lost vision. However, they only work if they are delivered at just the right stage of the disease. Timing is everything. To make sure that you catch wet AMD early, it is important to carefully monitor your vision with an Amsler grid (if the lines on the grid look wavy, you should see your doctor right away), and to schedule regular appointments with your eye doctor. FBC-funded researchers are developing a new microRNA test that would change the way wet AMD is detected.

What is microRNA? I bet you already know that your DNA is unique to you. In the 1950s, when DNA was first discovered by James Watson and Francis Crick, it was famously described as the “instructions” or the “blueprint” for each individual. Since then, the research community has made incredible strides forward in our basic understanding of the science of DNA. Today, we know that DNA is much more complicated than a simple set of instructions. This is because each new discovery about DNA raises multiple new questions. Sometimes these questions open up an entirely new area of science: like the relatively recent discovery of microRNA.

While we’ve known about DNA for more than half a century, microRNAs were only discovered about fifteen years ago. They were revealed by scientists who were studying DNA—in particular, the long stretches of DNA that seemed to code for nothing. What they learned is that rather than coding for nothing, this DNA codes for something called microRNAs. These molecules are produced in the cell and hundreds are secreted in body fluids such as the blood and vitreous. They leave a “signature” that can be detected with simple tests. MicroRNAs also have a very important role to play: they affect how genes are expressed.

Scientists have learned that specific microRNAs have the ability to turn the expression of genes on and off. They have also learned that detecting a specific microRNA signature can predict if someone will develop a particular disease. For example, microRNA diagnostic tests are the leading edge of advanced cancer screening approaches. Innovations in cancer diagnostics led FBC-funded Dr. Mike Sapieha and his colleague Dr. Vincent De Guire, a clinical biochemist at Hôpital Maisonneuve Rosemont, to ask if microRNAs could be used to help diagnosis the wet form of AMD. Their most recent results suggest that the answer is yes.

To investigate, they enlisted graduate student Catherine Ménard and collaborated with Dr. Flavio Rezende, a retinal specialist, who began collecting vitreous samples from patients who were being treated for wet AMD. The team studied the microRNAs that were present in these vitreous samples. Amazingly, they discovered a wet AMD disease “signature” involving three different microRNAs. After studying the vitreous, they discovered that this same signature could be detected using a basic blood sample. Using this microRNA signature, they were able to predict who had the wet form of AMD with 90% certainty!

These results are potentially game-changing because they could alter the standard of care for people living with AMD by enabling both predictive testing and early treatment. At this stage, Dr. Sapieha explains these results as “proof-of concept” because this study was the very first to detect a microRNA signature in both the vitreous and the blood. Moreover, it offers proof that a new kind of AMD test is possible. This proof allows the team to move to the next research step, which will involve a much larger, longer-term study of AMD patients. This clinical study will allow the team to ask two very important questions: 1) Will the microRNA signature change over time? And 2) Can the microRNA signature predict who will develop wet AMD?

Thanks to FBC-donors, doctors may soon be able to answer your question: will I develop wet AMD?

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