Researchers at Hôpital Maisonneuve-Rosemont show that obesity triggers an irreversible pathological inflammation that promotes the progression of age-related macular degeneration.
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness worldwide. Between 80 and 90% of this vision loss is caused by the neovascular form of AMD (also called wet form), that is, which is due to abnormal growth of new blood vessels under the macula (the center of the retina, very rich in photoreceptors).
Progression of this neovascularization leads to retinal edema or localized hemorrhage which over time leads to the death of photoreceptor cells essential for vision.
an inflammatory disease
In the early stages of AMD, deposits (called drusen) containing an amalgam of proteins, lipids, hydroxyapatite and certain metals form under the retina.
The abnormal presence of these drusen attracts the attention of the innate immune system, not only that already present in the retina, but also monocytes and macrophages which are recruited from the bloodstream to the site of the deposits.
The ensuing inflammation can then run amok and cause lesions that will create favorable conditions for the growth of new blood vessels and the development of neovascular AMD.
This contribution of inflammation to the progression of AMD means that the development of this disease can be influenced by certain lifestyle factors that generate conditions of chronic inflammation.
A good example is cigarette smoke, which is associated with a 2-3 times increased risk of AMD in people who smoke for many years. Obesity is another increasingly prevalent pro-inflammatory factor that appears to play an important role in the progression of AMD.
Studies show that patients with advanced AMD are more at risk of having excess visceral fat, and that a BMI > 30 is associated with an increased risk of seeing the disease progress more quickly.
Reprogram immunity
One of the most damaging effects of obesity is to create a climate of chronic inflammation which negatively influences the function of several organs (pancreas, muscles, heart, brain).
In other words, even if the visible manifestations of obesity are local, at the level of adipose tissue, it is the whole of the body which is susceptible to the attacks caused by excess fat.
It seems that it is exactly this phenomenon that would explain the increased risk of AMD observed in obese people (1).
In this study, the researchers noted that certain free fatty acids, the levels of which are increased in obesity, are able to modify the genetic program of innate immune cells (macrophages) present in adipose tissue and induce the expression of several pro-inflammatory genes (TNF, interleukin-1b and interleukin-6).
These reprogrammed macrophages can then be recruited to the eye where their pro-inflammatory activity will promote the progression of neovascular AMD.
A key point of the study is that this epigenetic reprogramming of innate immunity seems permanent, that is to say that the pathological inflammation that is triggered following the transformation of macrophages by excess fat is not not diminished following return to normal weight.
This shows how major the biochemical upheavals caused by obesity are and can cause serious long-term problems.
(1) Hata M et coll. Past history of obesity triggers persistent epigenetic changes in innate immunity and exacerbates neuroinflammation. Science 2023; 379: 45