Epigenetics and eye health II – Macular degeneration

At first you have a little trouble focusing, but you chalk it up to age. But then something strange happens – a hole appears in your field of vision. And strangely, it’s always right where you’re trying to focus, while the surrounding objects remain clear. You have trouble reading, watching TV, you can’t recognize your friends’ faces… This is how macular degeneration, a serious eye disease, manifests itself, which we’ll look at in the second part of our mini-series on eye health from an epigenetic perspective.

The human eye is a very complex structure and therefore a high number of genes are involved in its development and function – about 90% of those contained in our DNA. In order for everything to work as it should, the necessary genes must be switched on so that the organism can make proteins according to them. However, due to the environment, diet, lifestyle, and aging, a number of so-called epigenetic reactions take place in our bodies that negatively affect the activity of the genes in our DNA, which is reflected in an increased risk of eye diseases. In the first part of our miniseries we looked at cataracts from this perspective(https://www.epivyziva.cz/epigenetika-a-zdravi-oci-i-prevence-sedeho-zakalu/), today we will focus on macular degeneration.
The latter is one of the diseases in which epigenetic reactions play a major role. In fact, it is closely linked to ageing – its full name is “age-related macular degeneration”. The number of negative epigenetic marks on our genes generally increases with age, and those responsible for eye function are no exception. Others increase, for example, in connection with poor nutrition, lack of exercise, exposure to UV radiation, environmental toxins, smoking, etc.

What is macular degeneration?

Macular degeneration is a degenerative disease of the retina, which unfortunately manifests itself mostly in the area of the macula. This is an area with a high density of cones, i.e. light-sensitive cells, where the rays reflected from the objects we focus on fall. This is also why the ability to see in the centre of the field of vision is first impaired, while peripheral vision is preserved.
Often, people do not notice the development of the disease for a long time, attributing the impaired ability to focus to, for example, old-age hyperopia. In addition, if vision deteriorates in only one eye, the brain can “compensate” and vision deteriorates only slightly.
Macular degeneration comes in two forms. The most common (about 85% of cases) is the so-called dry form, which consists of a loss of retinal cells. It develops relatively slowly, but the treatment options are very limited – basically they consist of carotenoid administration. On the other hand, the wet form, which consists of blood vessels growing into places where they do not belong, is insidious in that it progresses very quickly – significant deterioration of vision (or even blindness) occurs within weeks or months. However, if caught early, it is treatable.

Is it free radicals?

Why are carotenoids given in the dry form of macular degeneration? The main reason is that they are powerful antioxidants that work effectively in the eye area. Damage to the structures of the eye by free radicals is a major contributor to macular degeneration (MD). But equally important is the influence of epigenetic reactions on gene activity. Scientific research has already demonstrated the existence of a number of epigenetic mechanisms and more will surely follow.
Moreover, even a lack of protection against free radicals may have an epigenetic background. In fact, in people suffering from the disease, scientists have discovered reduced levels of the enzymes glutathione S-transferases (PI, mu1 and mu5), which serve as scavengers of harmful oxygen free radicals. A deficiency of these enzymes thus leads to increased oxidative damage to the retina. At the same time, studies in people with MD have also shown increased methylation of the promoters of the genes by which these enzymes are produced. Methylation is one of the three basic epigenetic reactions – if it is increased in the area of the so-called promoters (the parts of DNA that start reading a certain gene), the activity of this gene decreases, and it may even be switched off completely.

However, other epigenetic links have also been demonstrated:

• Patients with MD have increased methylation in the region of the gene for interleukin C receptor 17, a substance important for cell signalling.
• People with MD have increased methylation of the genes that make clusterin and vitronectin in the body. These proteins prevent cells from breaking down, and if there is a deficiency of them in the body, it exacerbates the rate of inflammatory processes and can also lead to the development of MD.
• Another epigenetic reaction, histone acetylation, also plays a role. Histones are the proteins on which DNA strands are “wound”. Genes in a particular region can only be read if their histones are acetylated. If they are deacetylated, which is done by enzymes called deacetylases, the genes are switched off. But if we can reduce the amount of deacetylases, we increase the activity of genes that protect retinal cells from damage due to lack of oxygen, for example (this is particularly common in the wet form of MD).
• Differences in the production of so-called microRNAs – small chains of ribonucleic acids that can also block gene transcription – have also been shown. Some of them (for example microRNA 23) can increase the protection of cells against free radical damage, while others are involved in the regulation of inflammatory processes.
• In addition, some microRNAs are involved in reduced levels of the so-called CHF factor, which causes inflammatory degeneration of nerve cells. Interestingly, this mechanism is found not only in MD but also in Alzheimer’s disease.

What can help?

In light of the growing knowledge about the epigenetic causes of macular degeneration, scientists are already developing drugs that will work on the epigenetic principle (for example, the possibility of using microRNA 21 seems promising). At the same time, it is worthwhile to try to influence the level of epigenetic reactions in our body by diet and other lifestyle modifications.
In particular, we should focus on factors that affect the rate of overall ageing, because the rate of ageing is determined by the presence of negative epigenetic changes in our DNA.

• A healthy diet with plenty of antioxidants is important – a positive effect has been shown especially for the carotenoids lutein and zeaxanthin, which are found, for example, in egg yolks, corn, apricots, blueberries, walnuts, grape wine, curcurrants and other foods.
• The beneficial effect of anthocyanins (a dye found in berries) has also been confirmed.
• Research has also revealed a significant protective effect of regular fish consumption.
• Getting enough exercise is important.
• On the other hand, smoking (its influence on the development of MD has been demonstrated in studies on twins), excessive alcohol consumption and environmental toxins have negative effects.

Dietary supplements

Nutrients and herbs that combine antioxidant and epigenetic effects can also be of great service to us. If taken in high concentrations (i.e. in the form of dietary supplements), they can make a significant contribution not only to stopping macular degeneration, but also to healing the whole body.
Astaxanthin – this is a dye from the carotenoid family with a positive effect on the health of the whole eye. It has significant antioxidant potential and effectively reduces the level of free radicals in the eye area, but it also has epigenetic effects. For example, it influences the production of endothelial factors involved in blood vessel growth.
Omega-3s – consumption of two in particular, EPA and DHA, has been linked to the risk of macular degeneration. DHA in particular plays an important role in maintaining normal vision in general. In addition, it is used in the body to produce neuroprotectin D1, a substance with a strong protective effect on nerve cells, and is also important for maintaining optimal permeability and thickness of the cell membranes of rods and cones and for activating specific proteins in the retina.
Resveratrol, a powerful antioxidant with anti-inflammatory effects, regulates the activity of several genes related to the development of MD, protects retinal cells, influences the production of endothelial factor, which regulates the formation of new blood vessels (this is particularly important in the wet form of MD), and has an overall effect on slowing aging by influencing all the basic epigenetic reactions.
Rosemary – the extract of this herb has a significant antioxidant, anti-inflammatory and also epigenetic effect. For example, it very effectively protects retinal cells from damage (this is mainly due to the carnosol and carnosolic acid it contains).