Study links obesity to macular degeneration
a canadian studyone published in the magazine Science elucidates a new molecular mechanism that may cause age-related macular degeneration (AMD).
Research at the Hôpital Maisonneuve-Rosement in Montreal shows how life stressors, such as obesity, reprogram immune system cells and make them destructive to the eye as it ages.
“We wanted to know why some [individuals] with a genetic predisposition develop AMD, while others are spared,” said Przemyslaw (Mike) Sapieha, PhD, professor of ophthalmology at the Université de Montréal, in a statement. “Although considerable effort has been invested in understanding the genes responsible for AMD, variations and mutations in susceptibility genes only increase the risk of developing the disease, not cause it.”one
Sapieha is director of the Ocular Neurovascular Diseases Research Unit at the Maisonneuve-Rosemont Hospital Research Center associated with CIUSSS de l’Est-de-l’Île-de-Montréal. She also holds the Canada Research Chair in Retinal Cell Biology and Research Fund Chair in Ophthalmology at the Université de Montréal, and the Wolfe Professorial Fellowship in Translational Vision Research.
Additionally, Sapieha noted that while considerable effort has gone into understanding the genes responsible for AMD, variations and mutations in susceptibility genes only increase the risk of developing the disease, not cause it.
“This observation suggests that we need to gain a better understanding of how other factors, such as environment and lifestyle, contribute to the development of the disease,” he noted.
AMD is one of the leading causes of irreversible blindness worldwide, affecting approximately 196 million people in 2020. It comes in two forms:
- dry AMD, characterized by the buildup of fatty deposits in the back of the eye and the death of nerve cells in the eye,
- and wet AMD, which is characterized by diseased blood vessels that develop in the most sensitive part of the tissue that generates sight, called the macula.
Contact with pathogens
It is already known that the immune system in the eye of a person with AMD becomes dysregulated and aggressive. Normally, immune cells keep the eye healthy, but contact with pathogens like bacteria and viruses can cause them to go awry.
At the same time, immune cells are also activated when the body is exposed to stressors such as excess fat in obesity, making being overweight the number one non-genetic risk factor for developing AMD, after smoking.
In their study, Sapieha and Masayuki Hata, MD, PhD, used obesity as a model for accelerating and exaggerating stressors experienced by the body throughout life.
They found that transient obesity or a history of obesity leads to persistent changes in the DNA architecture within immune cells, making them more susceptible to producing inflammatory molecules.
Hata was a postdoctoral fellow in Sapieha’s lab. He is now an associate professor in the Department of Ophthalmology and Visual Sciences at the Kyoto University School of Medicine in Japan.
“Our findings provide important insights into the biology of the immune cells that cause AMD and will enable the development of more personalized treatments in the future,” Hata said in the news release.
The researchers hope their discovery will lead other scientists to broaden their interest beyond obesity-related diseases to other diseases characterized by increased neuroinflammation, including Alzheimer’s disease and multiple sclerosis.
Reference
1. Obesity linked to macular degeneration. Eurek alert. Press release. January 10, 2023. Accessed January 11, 2023. https://www.eurekalert.org/news-releases/976228