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Looking for links between the gut microbiome and eye disease

By Matt Wood The Forefront, UC Medicine

Over the past decade, researchers studying the human microbiome—the vast collection of bacteria, viruses and other microbes that live in our bodies—have discovered its many effects on health. Since much of our microbiome is concentrated in the digestive system, most of the attention so far has focused on its contribution to conditions like inflammatory bowel disease or the onset of food allergies.

But researchers at the University of Chicago are turning up evidence of the microbiome’s effects in new, unexpected places. They’ve discovered links between the microbiome and Alzheimer’s disease, organ transplant rejection, and effectiveness of cancer treatments. Now, Dimitra Skondra, MD, PhD, assistant professor of ophthalmology and visual science, is studying possible connections between the gut microbiome and eye disease.

Age-related macular degeneration (AMD) is the leading cause of vision loss, affecting more than 10 million Americans. It’s caused by the deterioration of the retina, the layer at the back of the eye packed with nerve cells that captures images and sends them to the brain. The retina is like a camera’s sensor, and its central portion, called the macula, is the most sensitive area responsible for focusing the center image of what we see.

When cells of the macula deteriorate, people start to get blurred or hazy vision. As the condition worsens, they can lose central vision altogether. There are no known causes for macular degeneration, although it’s more likely to occur in people over the age of 55. People with a family history of AMD are at higher risk as well. There is no cure for AMD, although lifestyle changes like healthy diet, exercise, and avoiding smoking can reduce risk.

“We know that genetics, lifestyle, diet, smoking, and where you live seems to affect disease development, but we really don’t know how they interact to determine who’s going to develop more advanced AMD,” Skondra said. “But we also know the gut microbiome plays a key role in metabolism, our immune system and lifestyle-induced changes in our body, so that’s how I began to think the two could be related.”

During her post-doctoral fellowship at Harvard, Skondra was studying the effects of a high-fat diet and how it worsens AMD symptoms in mice. She could see the impact clearly—even mice that weren’t genetically predisposed to AMD had worsening symptoms after a few weeks of a high-fat diet.

A light bulb moment

When she joined the UChicago Medicine faculty in 2016, she learned about research by Eugene B. Chang, MD, the Martin Boyer Professor of Medicine, who has shown how a high-fat dietcan disrupt the gut microbiome, increase inflammation and lead to inflammatory bowel disease and other immune disorders.

“It was like this light bulb moment,” Skondra said. “That’s why my mice 10 years ago got worse AMD, because the diet changed the microbiome. That was the missing link leading to more inflammation in the retina too.”

Since then Skondra has been establishing a new line of research at UChicago to see how changes in the microbiome influence AMD. She has been working with the Gnotobiotic Mouse Facilityat UChicago to develop the first germ-free mouse model of AMD. These mice are born and raised in sterile, germ-free environment so they have no bacteria at all. Germ-free models like this are considered the gold standard for microbiome studies because they’re a clean slate. Any changes to their microbiome are introduced deliberately and can be tracked with specific experiments.

“Now we can move forward to give them different diets, compare different genetic backgrounds and really break it down to differences in individual microorganisms,” Skondra said.

Skondra was recently selected as one of 20 Emerging Vision Scientists in the U.S. They visited Washington, DC, with the Association for Research in Vision and Ophthalmology in September to meet with members of Congress and discuss the importance of funding similar initiatives. She believes that more research on how the microbiome affects AMD and other eye diseases is crucial because it gets at the root of the problem, rather than just treating symptoms. If researchers can identify combinations of microbes or specific strains that put someone at risk for severe AMD, or perhaps identify a microbiome community that somehow prevents the disease, then they could develop probiotics or targeted antibiotics to steer it in the right direction. Her innovative approach to AMD has attracted attention, earning competitive regional and international grants.

“You cannot change the fact that you’re born with specific genetic mutations making you prone to AMD. You cannot change how you grew up and your lifestyle until a certain point in your life. But it’s very easy to manipulate the microbiome,” she said.

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