Researchers have made a breakthrough in researching one of the most common causes of blindness: they have identified a key element in the development of age-related macular degeneration (AMD). It is a protein that plays a role in the regulation of the immune system and is increasingly produced in AMD patients. The results could now lead to the development of new diagnostic and treatment methods, say the scientists.
Eyesight deteriorates more and more and in the worst case there is complete blindness: Millions of people worldwide are affected by age-related macular degeneration. This retinal disease typically only occurs at an advanced age. A distinction is made between two forms: In the dry version, pigment cells of the retina die. In the moist form, on the other hand, blood vessels grow into the retina and impair central vision. The progression of the moist form can be slowed down by special active ingredients, but so far there are no effective treatment options against the more common dry variant.
Research to date at AMD has shown that the emergence of both forms is based on a common root cause. It was already apparent that there are genetic predispositions that are associated with an increased risk of illness. There were also indications that the development of the immune system is based on malfunctions in the eye. Against this background, an international team of researchers has now focused on the possible meaning of a protein called FHR-4. It has a function in the so-called complement system, which plays a role in inflammation and defense against infections.
A key element is emerging
By examining the blood of 484 AMD patients and 522 control persons of the same age, the researchers were able to prove that the disease is associated with a significantly increased concentration of FHR-4 in the blood. Apparently, the protein also accumulates intensely in the eye, after which results were obtained from eye tissue donated for medical purposes. FHR-4 is therefore particularly high in the macula – the eye region affected by the disease. “So far there has only been evidence of a possible role for FHR proteins. Now we have been able to demonstrate a direct connection, ”says co-author Simon Clark from the University of Manchester.
The researchers then carried out a so-called genome-wide association study to identify genetic peculiarities that could be linked to the increased FHR-4 level in AMD patients. They found that higher levels of FHR-4 in the blood are linked to changes in genes that are responsible for the production of proteins of the so-called factor H family. These genes lie closely together on chromosome 1 of the human genome, the researchers report. According to them, the identified genetic peculiarities also fit genetic variants that were linked to an increased risk of AMD in earlier studies.
Hope for new diagnostic and treatment methods
The bottom line of the results now shows that inherited genetic changes lead to an increased FHR-4 level in the blood, which can then cause an uncontrolled activation of the immune reactions in the eye, which is at the beginning of the development of the two forms of AMD. “The combined protein and genetic findings now provide convincing evidence that FHR-4 plays a key role in the part of the immune system that affects the eyes,” said co-author Paul Bishop of the University of Manchester.
As he and his colleagues explain, the results now provide important starting points for further research and especially for the development of new diagnostic and treatment methods. “Aside from a better understanding of the development of AMD, this work shows a way to predict the risk of the disease by measuring the concentration of FHR-4 in the blood. There is also a new path to treatment by lowering FHR-4’s blood levels to correct the function of the immune system in the eyes, ”says Bishop.
His colleague Valentina Cipriani from Radboud University in Nijmegen adds with a view to the future: “We also hope that our results will now arouse the interest of other research groups, so that they can help clarify the role of the complement system in the development of the disease”, says the scientist.
Source: Queen Mary University of London, professional article: Nature Communications, doi: 10.1038 / s41467-020-14499-3