When the immune system attacks the retina

Whe exact age-related macular degeneration, the most common cause of old age blindness in the western world, is still largely unknown. However, the so-called complement system, an ancient branch of the immune system, is under urgent suspicion. However, it has so far been unclear which of the numerous members of this family of immune proteins add to the retina in such a way that blindness can occur.

Researchers led by Simon Clark from the Center for Ophthalmic Research at the University of Tübingen could now have succeeded in exposing one of the ringleaders of severe retinal disease. We are talking about a protein from the ranks of the complement system with the bulky name “Factor-H-Related Protein-4”, or FHR4 for short. As Clark says on request, he originally had no intention of investigating the causes of macular degeneration. His actual research area, which he has been dealing with for many years, is the complementary system. In connection with this, he wanted to clarify one day exactly where FHR4 is located in the body. “To do this, we developed an antibody against FHR4 and used it to search for the immune protein in more than 50 human tissues.

We found it in the eyes, among others, but only in some people – and only those with age-related macular degeneration, ”explains the biochemist. In further investigations, they would have discovered that FHR4 is only produced in the liver. “Since it must have got into our eyes from there, we had the idea of ​​searching for FHR4 in the blood.”

The scientists have achieved this goal in the current study, the results of which have now been published in the journal “Nature Communications”. A comparison of the blood values ​​of around 500 patients with age-related macular degeneration and roughly the same number of people without eye problems then confirmed their suspicion. As Valentina Cipriani of Queen Mary University in London, Simon Clark and the other study authors report, the blood of the eye-sick men and women contained much more FHR4 than that of the healthy controls.

The retina of a healthy eye.


In-depth genetic analyzes then revealed another surprise: People with a large amount of FHR4 in the blood were conspicuously often carriers of genetic variants that are associated with a high risk of age-related macular degeneration. “As our observations show, these genetic varieties influence the blood content of FHR4,” Clark explains, adding: “However, they are not in the FHR4 gene, as you would expect, but in that of another complement protein, namely Factor H (FH). We were very surprised. “

Leaky blood vessels give off FHR4 proteins

But why does the immune protein FHR4 accumulate in the eye and is causing trouble here? The British biochemist most likely considers the following scenario: In advanced age, when the small blood vessels become increasingly leaky, FHR4 flows more and more from the blood into the back of the eye, causing inflammatory reactions. The greater its content in the blood, the more likely it is to damage the retina. “People with very high levels of FHR4 in the blood all had macular degeneration,” Clark explains. The immune protein does not infiltrate the back of the eye to combat pathogens there. The main task of the complement system is to ward off such intruders. With age-related macular degeneration, there is no evidence of infection.

Frank Holz from the University Eye Clinic in Bonn describes the findings of Clark and his colleagues as new and interesting. “So far, however, there are no therapy studies that build on this,” admits the ophthalmologist. Other complement inhibitors are already further in this regard. However, one of them, an antibody against factor D, was not effective.

However, an inhibitor against another complement protein (C3) has given promising results in a small study and is currently being tested in a large study. “If it proves itself, many patients with the” dry “late form of age-related macular degeneration could be offered effective therapy for the first time. So far, this has only been possible for people with the “wet” late form, “says Holz. As far as terminology is concerned, the second variant is usually the consequence of the first: For reasons unknown so far, some people develop small vessels in the back of the eyes that have been damaged, which grow into the retina. They transform the previously “dry” defect into a “wet” one. Since the new blood streams are very permeable and bleed easily, they can permanently impair vision. Such a fate can often be averted with drugs that suppress pathological vascular growth.

However, no effective remedy has yet been found against the various “dry” types of age-related macular degeneration, which make up around 80 to 90 percent of cases of illness. Contrary to the common term age-related macular degeneration, this diagnosis hides very different ailments. The results of the new study also show this. For example, only about 30 of the eye-sick people had elevated levels of FHR4 in the blood. For the rest, the demise of the retinal cells is likely to have other causes.

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Detect and Treat Macular Degeneration | NDR.de – Guide

As at: 02/24/2020 05:07 p.m.

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Macular degeneration is an incurable disease of the retina.

Up to four million Germans suffer from age-related macular degeneration (AMD). This incurable retinal disease is the most common cause of severe visual impairment in people over 60 in Germany. Gradually, the sensory cells lose their function at the point of sharpest vision (macula) so that those affected no longer recognize what they are looking at directly.

Causes of dry and wet macular degeneration

There are two types of AMD: the “dry” and the “wet”.

  • Around 80 percent of patients suffer from dry AMD. It arises from deposits under the retina, which cannot be effectively treated with medication, but do not always lead to a drastic visual impairment. Studies show that a vitamin-rich diet can slow macular degeneration and that the macula is primarily dependent on the supply of the building materials lutein, zeaxanthin and omega-3 fatty acids. Regular intake of these substances ensures more stable pigmentation in the eye. Overall, a targeted diet with lots of green vegetables, berries and fish can have a positive effect on the dry form of macular degeneration. Many sufferers also take food supplements that contain these substances. However, there is no clear proof of effectiveness.
  • Wet AMD is much more aggressive: pathological blood vessels develop under the retina that secrete fluid. Bleeding and water retention occur in the retina. Visual cells die, the center of vision is severely damaged.

Symptoms of macular degeneration

While those with a dry AMD primarily notice increasing shading in the central area, the first sign of wet macular degeneration is rather distorted vision: straight lines, for example the tile joints in the bathroom, appear crooked, letters become blurred.

Wet macular degeneration: therapy with syringes

The course of a wet AMD can be slowed down by injections into the eye and can often be stopped for years. Under local anesthesia, the ophthalmologist regularly injects a drug directly into the vitreous of the eye. The active substance, a so-called VEGF antagonist, inhibits the growth factors that are responsible for vascular proliferation in the retina. This stops the progression of the disease and in some cases even improves eyesight. However, not every active ingredient is tolerated equally well by everyone affected, so ophthalmologists sometimes have to search for the optimal medication for a while. A brand new product is a drug with the active ingredient brolucizumab, the effect of which is said to last longer than the previously available preparations.

Further information

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Ask the ophthalmologist Dr. Andrea Hassenstein Your questions about macular degeneration. The chat starts on February 25th at 8:45 p.m. and lasts 30 to 45 minutes.
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Tools for special everyday requirements

There are various aids for those affected:

  • In the case of dry macular degeneration or after successful syringe therapy of wet macular degeneration, an artificial lens (SML lens) can be used as an aid, which enlarges the point of sharpest vision. However, this intervention is not a cash benefit, so those affected have to bear the costs themselves.
  • With telescope glasses, activities such as playing a musical instrument are still possible.
  • Magnifying glasses make reading possible.

Risk factors for macular degeneration

The risk factors for the development of age-related macular degeneration include smoking, eye strain from UV radiation as well High blood pressure. Genetic predisposition also plays a role. Especially people with fair skin and blue eyes are affected more often with increasing age.

Prevent with regular examinations

Since the treatment cannot cure the disease but can only stop it, the most important thing is timely diagnosis of macular degeneration. Experts therefore recommend having an ophthalmologist’s examination every two years from the age of 40.

Detect signs of AMD with test

The first signs of an AMD can be seen using the Amsler grid testing determine yourself. The test does not replace a visit to the doctor.

Further information

According to a study, the light from LED lamps can promote age-related macular degeneration. But the risk of damage to the retina can be reduced.
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Active substances derived from algae could help as a medicine for a special form of macular degeneration. The so-called fucoidans are currently still being researched.
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In cataracts, the cloudy eye lens is replaced by an artificial lens in one operation. A study shows that those who have surgery see better and live longer.
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Experts on the subject

Priv-Doz. Dr. Ulrich Schaudig, chief physician
Eye clinic
Asklepios Klinik Barmbek
Rübenkamp 220
22291 Hamburg
(040) 18 18-82 28 31
www.asklepios.com

Priv-Doz. Dr. Andrea Hassenstein, senior physician
Clinic and polyclinic for ophthalmology
University Medical Center Hamburg-Eppendorf
Martinistrasse 52
20246 Hamburg
www.uke.de/kliniken-institute/kliniken/augenheilkunde

Further information
Do I have AMD? Amsler Grid Test
The first signs of AMD can be determined with the simple test.
https://www.dbsv.org/

AMD – Medical-Social Network
Medical-social network for the disease of age-related macular degeneration.
https://www.amd-netz.de/

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25.02.2020 | 8:15 p.m.

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