New Research from Canada and France: Can Your Gut Microbes Influence the Development of Wet Macular Degeneration?

Photograph of a retina with wet age-related macular degeneration — A retina with wet AMD

New research From Canada and France reveals that microbes in the gut might play an important role in the development of wet age-related macular degeneration (AMD). These findings indicate that it might be possible to prevent, or delay the development of, wet AMD by changing the balance of microbes in the gut through diet or other means.

According to study co-author Przemyslaw Sapieha, from the University of Montreal and McGill University, “Our research suggests that diets rich in fat alter the gut microbiome in a way that aggravates wet AMD. 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 its progression.”

From EMBO Molecular Medicine

The research, entitled Gut microbiota influences pathological angiogenesis in obesity-driven choroidal neovascularization (explained below), has been published “online first” in the November 15, 2016 edition of EMBO Molecular Medicine. EMBO Molecular Medicine is a peer-reviewed, online, open-access journal dedicated to research that combines clinical research and basic biology in a number of areas, including aging, genetics, gene therapy, immunology and inflammation, sensory defects, stem cells, and regenerative medicine.

The authors are Elisabeth Andriessen, Ariel Wilson, Gaelle Mawambo, Agnieszka Dejda, Khalil Miloudi, Florian Sennlaub, and Przemyslaw Sapieha, who represent the following institutions: the University of Montreal, Quebec; the Polytechnic School of Montreal; McGill University, Montreal; Pierre and Marie Curie University, Paris, France; and the French National Institute of Health and Medical Research, Paris.

First, Some Terminology

Here is a brief explanation of some key terms used in the research:

Microbiota: Microorganisms that typically inhabit a particular environment, such as the soil, a body of water, or a site on – or in – an organism. In this case, gut microbiota refers to the microorganisms found in the digestive tract/intestines.
Angiogenesis: Describes the growth of new blood vessels and plays a crucial role in the normal development of body organs and tissue. Sometimes, however, excessive and abnormal blood vessel development can occur in diseases such as cancer (tumor growth) and macular degeneration (retinal and macular bleeding).
Choroidal neovascularization: In wet macular degeneration, the choroid, a part of the eye containing blood vessels that nourish the retina, begins to sprout abnormal new blood vessels that develop into a cluster under the macula (neo = new; vascular = blood vessels).

About the Research

Excerpted from Gut microbes influence development of wet AMD, via Medical News Today:

[The research team] used [a mouse model of AMD] 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 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. “Our study suggests that diets rich in fat alter the gut microbiome in a way that aggravates wet AMD. 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 [its progression],” says [study author] Przemyslaw Sapieha.

About Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a gradual, progressive, painless deterioration of the macula, the small sensitive area in the center of the retina that provides clear central vision. Damage to the macula impairs the central (or “detail”) vision that helps with essential everyday activities, such as reading, preparing meals, watching television, playing card and board games, and sewing.

AMD is the leading cause of vision loss for people aged 60 and older in the United States. According to the American Academy of Ophthalmology, 10-15 million individuals have AMD and about 10% of people who are affected have the “wet” type of AMD.

Wet (Neovascular) Macular Degeneration

In wet AMD, the choroid (a part of the eye containing blood vessels that nourish the retina) begins to sprout abnormal new blood vessels that develop into a cluster under the macula, called choroidal neovascularization (neo = new; vascular = blood vessels).

Because these new blood vessels are abnormal, they tend to break, bleed, and leak fluid under the macula, causing it to lift up and pull away from its base. This damages the fragile photoreceptor cells, which sense and receive light, resulting in a rapid and severe loss of central vision.

What are the Risk Factors for Macular Degeneration? An Answer from Lylas G. Mogk, M.D.

Dr. Mogk is the is the author of Age-Related Macular Degeneration (AMD) on the VisionAware website; founding director of the Center for Vision Rehabilitation and Research, part of the Department of Ophthalmology at the Henry Ford Health System in Michigan; and co-author of Macular Degeneration: The Complete Guide to Saving and Maximizing Your Sight.

To understand what the risk factors are and what we can do to lower our risk for age-related macular degeneration, it’s helpful to understand how macular degeneration develops.

First, advanced age and long-term environmental exposures together produce an increased number of free radicals: unstable molecules that damage the macula if they are not immediately neutralized by anti-oxidants.

Next, this initial damage causes inflammation; the inflammation then causes more damage, which results in more inflammation and the cycle continues, eventually scarring the macula and causing central vision loss.

To reduce the risk of AMD, we need to decrease our exposure to toxins, neutralize the free radicals that are produced by exposure to toxins, and decrease our inflammatory response. We can do that by addressing the first six of the ten risk factors listed below.

Top 10 Risk Factors for Developing Age-Related Macular Degeneration

The six risk factors we can control:

Smoking: Current smokers have a two-to-three times higher risk for developing age-related macular degeneration than people have who never smoked.
Artificial fats: Usually labeled “partially-hydrogenated vegetable oils,” these artificial fats are pervasive in foods and particularly in low-fat bakery goods. Low-fat foods are good options if they’ve achieved their low-fat status through a process that physically removes the fat, as in skim milk or low-fat cottage cheese. Low-fat bakery goods are different, however. If you remove all or half the fat from a cake recipe, it won’t turn into a cake; thus, when cakes and bakery goods are labeled low-fat or no-fat, it means they contain artificial fats, or laboratory-produced chemicals. These chemicals are not food and our bodies can’t metabolize them.
Sunlight: It is the blue wavelengths from the sun that damage the macula, not the ultraviolet (UV) rays. Read Helpful Non-Optical Devices for Low Vision: Absorptive Sunglasses for more information.
A diet high in processed, packaged foods and low in fresh vegetables: Vegetable oils are added in the packaging process. These oils are rich in omega-6 fatty acids, which promote inflammation.
Uncontrolled hypertension and high cholesterol: Research by the National Eye Institute indicates that persons with hypertension are 1.5 times more likely to develop wet macular degeneration than persons without hypertension.
Obesity: Being overweight doubles the risk of developing advanced macular degeneration.

The four risk factors we can’t control:

Advanced age: Although AMD may occur earlier, studies indicate that people over age 60 are at greater risk than those in younger age groups. For instance, a large study found that people in middle age have about a 2% risk of getting AMD, but this risk increased to nearly 30 percent in those over age 75.
Race: Whites are much more likely to lose vision from age-related macular degeneration than are Blacks or African-Americans.
A gene variant that regulates inflammation: While not all types of macular degeneration are hereditary, certain genes have been strongly associated with a person’s risk of age-related macular degeneration, and genetic predisposition may account for half the cases of age-related macular degeneration in this country.
Family history: Studies indicate that your chances of developing age-related macular degeneration are three to four times higher if you have a parent, child, or sibling with macular degeneration.

You can read more about risk factors for AMD and actions you can take at Risk Factors for Age-Related Macular Degeneration (AMD).

More about the Study from EMBO Molecular Medicine

Edited and excerpted from the study Abstract and Introduction, with the full article available online:

Age-related macular degeneration in its neovascular form (NV AMD) is the leading cause of vision loss among adults above the age of 60. Epidemiological data suggest that in men, overall abdominal obesity is the second most important environmental risk factor after smoking for progression to late-stage NV AMD.

To date, the mechanisms that underscore this observation remain ill-defined. Given the impact of high-fat diets on gut microbiota, we investigated whether commensal [i.e., a symbiotic relationship in which one species is benefited while the other is unaffected] microbes influence the evolution of AMD.

Using mouse models of NV AMD, microbiotal transplants, and other paradigms that modify the gut microbiome, we uncoupled weight gain from confounding factors and demonstrate that high-fat diets exacerbate choroidal neovascularization (CNV) by altering gut microbiota.

Gut dysbiosis [i.e., microbial imbalance] leads to heightened intestinal permeability and chronic low-grade inflammation characteristic of inflammaging [i.e., low-grade chronic systemic inflammation established during physiological aging] with elevated production of IL-6, IL-1ß, TNF-a, and VEGF-A that ultimately aggravate pathological angiogenesis.