New research reveals that microbes in the gut play an important role in the development of neovascular or wet age-related macular degeneration.
In the journal EMBO Molecular Medicine, researchers report how they used mice to show that a high-fat diet can cause an imbalance in gut microbes that leads to more permeable intestines, chronic low-grade inflammation, and ultimately increased formation of new blood vessels under the retina - a feature of advancing wet age-related macular degeneration (AMD).
The team - led by Przemyslaw (Mike) Sapieha, a professor at the University of Montreal in Canada and a researcher in Montreal's Hôpital Maisonneuve-Rosemont - suggests the findings mean it may be possible to prevent or delay wet AMD by changing the balance of microbes in the gut through diet or other means.
AMD is a leading cause of vision loss among seniors. As the disease progresses, it blurs the sharp, central vision we need for seeing objects directly in front of us, such as reading, driving, sewing, and using a computer or mobile device.
AMD ranks third among the global causes of visual impairment and is the primary cause of visual deficiency in industrialized nations. Around 10 million people in North America are living with AMD.
The disease affects the macula - a part of the retina lining the back of the eye that allows us to see fine detail. In AMD, the immune system is more active, and the retina contains larger-than-normal deposits of fat debris called soft drusen. As the disease progresses the macula becomes increasingly damaged.
High-fat diets alter gut microbiome to aggravate wet AMD
There are two main forms of AMD, called dry AMD and neovascular or wet AMD. In wet AMD - the subject of this study - the eye develops new diseased blood vessels under the retina.
- Smoking doubles the risk of developing AMD
- White people are at higher risk of developing AMD than other ethnic groups
- Changing lifestyle choices - such as not smoking, adopting healthy diet, and taking regular exercise - may reduce the risk.
While wet AMD only accounts for around 10 percent of AMD, it is the primary form leading to blindness. Current treatments become less effective with time, so it is important to find new ways to prevent the debilitating condition.
The team behind the new study notes that while evidence points to overall abdominal obesity in men as a risk factor for progression to late-stage wet AMD, there is little understanding about the underlying mechanisms. Given there is also evidence that high-fat diets affect gut microbes - collectively known as the gut microbiome - they decided to investigate whether this might explain the link.
For their study, the researchers carried out a series of experiments using a mouse model of wet AMD. These included transplanting gut microbes from mice fed a normal diet and mice fed a high-fat diet into normal-weight AMD mice. They did this to eliminate the potential for obesity to directly influence the results.
The results showed that high-fat diets appear to hasten the formation of new blood vessels in the wet AMD mice by altering the gut microbiome.
The researchers suggest the altered gut microbiome leads to increased permeability of the intestines and chronic low-grade inflammation. This is accompanied by raised production of pro-inflammatory cell signaling proteins (cytokines) and ultimately leads to generation of new blood vessels seen in advanced wet AMD.
"Our study suggests that diets rich in fat alter the gut microbiome in a way that aggravates wet AMD, a vascular disease of the aging eye. Influencing the types of microbes that reside in your gut either through diet or by other means may thus affect the chances of developing AMD and progression of this blinding disease."
Prof. Przemyslaw Sapieha