Macular degeneration, epigenetics and immunity

Researchers at the US National Institutes of Health, working under the leadership of Dr. Robert Nussenblatt, have concluded that epigenetic changes caused by external factors such as smoking, diet and aging can affect the expression of immune system genes. This, in turn, can lead to the development of age-related macular degeneration. This work is the first epigenetic study revealing the molecular mechanisms of the development of eye diseases.

Age–related macular degeneration leads to the destruction of photosensitive cells of the macula - the central region of the retina. As the disease progresses, a person first loses central vision, after which he gradually develops complete blindness. Existing treatment methods can slow down the development of some forms of macular degeneration, but the disease is incurable.

In recent studies, scientists have identified several genes whose mutations increase the risk of macular degeneration. In addition, it is believed that exposure to external factors can also increase the risk of various diseases. One explanation for this phenomenon is that environmental influences can affect the profile of DNA methylation – a chemical modification that blocks gene activity – which, in turn, alters gene expression. This can lead to an increase or decrease in the production of certain proteins. The involvement of such changes in pathogenesis has been proven for a number of diseases, including cancer, systemic lupus erythematosus, multiple sclerosis and others.

In order to study the role of DNA methylation changes in the development of macular degeneration, the authors examined three pairs of twins – one pair of identical and two pairs of fraternal – in which only one of the siblings developed age-related macular degeneration. Identical twins have identical genotypes, whereas the genes of fraternal twins are identical by about 50%, which makes it possible to assess the influence of the external environment on the nature of gene methylation.

Comparison of DNA methylation profiles of twins showed that age-related macular degeneration was associated with changes in the methylation levels of 231 genes. Among them was a gene encoding the C receptor for interleukin 17. A decrease in the level of methylation of this gene was accompanied by an increase in its activity and, accordingly, an increase in the expression of the interleukin 17 receptor C on circulating immune cells of siblings with macular degeneration. The results of the analysis of the expression level of this receptor in the blood and, most importantly, in the retina of 202 patients with this disease and 96 people in the control group confirmed the revealed pattern.

The function of interleukin 17 is to stimulate immune responses that develop in response to the penetration of infectious agents into the body, in particular fungi. The researchers concluded that immune responses triggered by this protein can lead to the development of macular degeneration. They believe that the assessment of the activity of the C receptor gene to interleukin 17 in patients at high risk for the development of age-related macular degeneration can be used as a method of early diagnosis of the disease.

In the near future, the authors plan to find out which environmental factors may be responsible for increasing the activity of the C receptor to interleukin 17 and how to restore the epigenetic profile, the violation of which leads to the development of chronic inflammation in the retina and macular degeneration. They are also going to study the role of epigenetic changes in the development of other eye diseases.

Article by Lai Wei et al. Hypomethylation of the IL17RC Promoter Associates with Age-Related Macular Degeneration is published in the journal Cell Reports.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the National Institutes of Health:
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29.11.2012