23 March 2018

Microglia is being restored

According to a study by the National Institute of Eye Diseases as part of the National Institutes of Health, microglia cells – the brain's immune system – can regenerate in the retina after their death. This discovery can be used for the treatment of currently incurable slowly progressive inflammatory diseases of the retina, for example, retinitis pigmentosa or age-related macular degeneration.

The inflammatory process is the main cause of the death of nerve cells in diseases of the retina. Containment of immune system cells is of great importance in the development of treatments for retinal degeneration.

The retina is a thin layer of nerve cells lining the inside of the back wall of the eyeball. In addition to photoreceptors (rods and cones) that perceive visual information, it contains several layers of neurons. Macrophages of the nervous system – microglia – ensure the work of photoreceptors and maintain the health of the retina.

Retinal microglia of healthy adult mice.
Here and further source: Wai T. Wong, National Eye Institute.

In a healthy eye, microglial cells interact with other retinal neurons and help them perform their functions, in particular, transmit information to the brain. When the retina is damaged, microglial cells migrate to the epicenter and remove defective and dead neurons. In this case, healthy cells can also be destroyed by mistake, which is accompanied by loss of vision. Studies show that excessive activity of microglia contributes to the progression of age-related macular degeneration and retinitis pigmentosa, and its suppression or removal slows down the process of retinal degeneration.

However, microglia is necessary for the normal functioning of the retina, so it is very important to "return" it at the end of treatment.

A group of researchers led by Dr. Wai T. Wong became interested in the question of what happens in the retina after microglia removal. In particular, they wanted to find out whether the cells could return to normal life and perform their functions. To do this, the mice were injected with an experimental drug PLX5622 (Plexxikon), which blocks the CSF-1 receptor on the surface of glial cells. This receptor is vital for microglia, its blocking leads to cell death. As a result, the microglia almost completely disappeared, leaving a small group of cells around the exit site of the optic nerve.

Short-term loss of microglia does not disrupt the function of the retina, so it can be used as a method of treating diseases accompanied by an inflammatory reaction. A longer absence of microglia led to an aggravation of inflammation and a violation of the immune response.

Thus, in order to consider the suppression of inflammation as a method of retinal treatment, it is necessary to restore microglia in time. Immunity can be put on pause, but then it must be "started" again.

The researchers observed mice after discontinuation of the PLX5622 course. After 30 days, the retina was already "dotted" with glial cells, and after 150 days, the microglia completely recovered.


Dynamics of retinal changes during treatment with a drug that eliminates microglial cells. Immediately after the termination of the course, microglia is almost completely absent. After 7 days, microglial cells migrate to the retina, by day 10 their number continued to grow.

Modern methods of retinal imaging have made it possible to determine that microglia was restored first near the exit point of the optic nerve, and then spread evenly to the entire retina.

Surprisingly, despite the complex organization of the immune system, it is restored both quantitatively and qualitatively – the cells begin to function normally.

In order to test the work of the new microglia, the researchers simulated retinal trauma by exposure to bright light. New cells were activated and migrated to the site of injury. In addition, the method of fixation of electrical impulses of neurons (electroretinography) showed that the microglia was able to interact with other neurons.

These experiments prove the safety of the treatment of inflammatory and degenerative diseases of the retina by the method of short-term suppression of inflammation.

In the studies already conducted, the experimental drug PLX5622 was administered systematically to animals. The next step is to develop forms for local administration in order to reduce its effect on the central nervous system, which also has microglia.

Article by Y. Zhang et al. Repopulating microglia restore endogenous organization and function under CX3CL1-CX3CR1 regulation is published in the journal Science Advances.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru according to NIH materials: Immune cells in the retina can spontaneously regenerate.

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