Macular degeneration, a condition that leads to vision loss, affects millions of Americans every year. It occurs when individuals develop an overgrowth of blood vessels that impact the function of the eye. Recently, University researchers discovered that exercise prior to the development of macular degeneration caused a decrease in blood vessel overgrowth in laboratory mice.
Age-related macular degeneration impacts individuals over the age of 50 and compromises their central vision, forcing patients to rely on peripheral vision and complicating their daily tasks.
A majority of individuals have a form of AMD known as non-neovascular, or dry AMD, in which the yellow debris collects in the center of the retina — a layer of nerve cells that sense light and communicate with the brain. Dry AMD may result in the death of photoreceptor cells and causes gradual vision loss. Macular degeneration arises from the yellow debris from dry AMD, otherwise known as drusen, which can initiate growth factors and lead to the wet or neovascular form of AMD. The growth factors cause an overgrowth of blood vessels under the retina — known as choroidal neovascularization — and leads to a severe loss of central vision.
Bradley Gelfand, assistant professor in the University's Department of Ophthalmology, noted an interest in exploring the connection between exercise and macular degeneration after analyzing the results of a 2017 meta-study that combined self-reported health behaviors of numerous patients.
“The meta-analysis found that there was a very significant reduction in the prevalence of macular degeneration in people who had self-reported as having engaged in some kind of exercise,” Gelfand said.
Gelfand noted that a major limitation of the meta-study was that participant data was self-reported, which could lead to less accurate results.
“We are a translational research lab, so we're very interested in cellular and animal models of macular degeneration,” Gelfand said. “We were inspired by these clinical studies to study the relationship between exercise and macular degeneration in a far more precise and controlled way.”
Furthermore, Zhen Yan, professor of cardiovascular medicine and co-author of the study, expressed an overarching interest in the benefits of exercise. He noted that unlike medications that are often tailored to a specific disease or disorder, exercise could help prevent the development of multiple conditions.
“I'm passionate about the benefits of exercise to any disease,” Yan said. “One type of exercise or [a combination] of exercises can be beneficial to many diseases. I can't find any drug that will have multiple positive impacts.”
To assess the effect of exercise on macular degeneration, researchers divided laboratory mice into two groups. One group of mice did not have access to a running wheel while the other group was placed in cages with running wheels. The mice exercised for four weeks before the pathological blood vessels were induced.
Blood vessel growth was stimulated in the mice using a practice called laser-induced choroidal neovascularization in which a laser beam causes a thermal injury burn, puncturing the back of a mouse’s eye. In turn, pathological vessels spontaneously grow, and these vessels share similarities to the blood vessel overgrowth seen in patients with wet macular degeneration.
After analyzing the initial impact of exercise, the researchers replicated the study to ensure the validity of the results.
“We did our first study, and we saw about a 45 percent reduction in the pathological growth of these blood vessels [in the exercising laboratory mice],” Gelfand said. “In the second study, we again saw a very significant decrease in blood vessel growth, and that gave us very strong confidence that what we were seeing was a real effect.”
Although researchers saw a significant benefit from exercise, they are still unsure about the underlying mechanisms which cause these results and acknowledge that this is a potential area for future research.
Yan also noted that researchers questioned the impact of exercise before and after the introduction of the disease. Their findings indicate exercise only had a significant benefit when mice engaged in this behavior prior to injury.
“The other study we did was we initiated exercise immediately after the procedure, and it didn't have an impact, suggesting that it is the preconditioning — or the exercise training before the establishment of the model — that was effective in reducing the injury,” Yan said.
Additionally, the team mentioned the potential of testing the impact of other exercise behaviors on the growth of pathological blood vessels.
“My lab has recently developed a novel voluntary weightlifting model for mice,” Yan said. “We can, presumably, subject mice to weightlifting training, which is more translatable to weight training in humans and study the impact of resistance exercise on this condition.”
If these behaviors were tested, the study would follow a similar model where mice are subjected to four weeks of exercise prior to the introduction of macular degeneration and the associated benefits would be investigated.
Gelfand also mentioned that the laboratory mice ran eight kilometers per day on average which is a significant distance for a small subject. In the future, the team would like to investigate the minimum amount of exercise required to see a benefit for macular degeneration.
With the hope of transferring knowledge from the study of lab mice to human research, Gelfand emphasized that individuals should speak to their physicians before starting any form of exercise.
“Before anybody starts going out and exercising, [they should] talk with their doctor to make sure that it's a safe and healthy thing for them to do,” Gelfand said. “They can discuss what kinds of exercises might be the best for them.”
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