30 August 2018

Retinal self-repair is possible

A new method has given blind mice the ability to see light

Yulia Vorobyova, Vesti

But its essence lies in the activation of special retinal cells, which are very similar in properties to stem cells.

Recall that the retina is the thin inner shell of the eye. It contains photoreceptor (i.e. light-sensitive) cells. They come in two types: rods, which are responsible for vision at dusk and at night, as well as for peripheral vision, and cones, three types of them, each excited by light of a certain wavelength, are responsible for color perception during the day.

In degenerative diseases of the retina, the work of these cells is disrupted. And effective treatment of such ailments has not yet existed.

In the course of the new work, scientists decided to use the regenerative abilities of the body, in other words, the function of "self-repair". In their opinion, this direction is more promising than treatment with medications or invasive procedures.

The object of the study was Muller cells – these are auxiliary cells of nervous tissue that are contained in the retina of vertebrate eyes.

Previous studies have shown that in danio-rerio fish (one of the model organisms), Muller cells demonstrate amazing regenerative potential. When damaged, they begin to divide and, like stem cells, can serve as precursors of photoreceptor and other types of retinal cells.

But in mammals, Muller cells do not have this ability. That is why progressive retinal diseases (for example, age-related macular degeneration or retinitis pigmentosa) become irreversible in humans.

But what if human retinal cells had the same ability to "self-repair" as the danio-rerio? It is possible to achieve this if we carry out the so-called gene transfer and "reprogram" cells, scientists are sure. (They felt that it would be counterproductive to cause the division of Muller cells with damage.)

The new method was tested on mice. Rodents blind from birth were first activated by dormant Muller "stem" cells, and then, with the help of gene transfer, they were forced to develop into photoreceptor rod cells.

Experts note that rods are the most common type of cells in the retina, their restoration is the first step to the perception of light. It is the rods that transmit signals to other cells deep into the retina through synapses, which are then sent to the brain.

"Sticks allow us to see in low light, but they can also help preserve cones, which are important for color vision and high visual acuity. Cones tend to die in the later stages of eye diseases. If we get the opportunity to restore the rods, this may be a strategy for treating eye diseases," explains Thomas Greenwell from the US National Eye Institute.

The team found that with their approach, the new rods successfully integrate into the structure of the retina and begin to function. There was no difference between these "generated" cells and the "native" ones, the researchers write. The new sticks reacted to light and transmitted signals to other cells, which then entered the visual cortex of the mice's brain (this was confirmed by measurements of brain cell activity). Thus, the visual pathway was restored.

Four to six weeks after the "reprogramming" of Muller cells, blind rodents could already see light, but they probably did not distinguish objects or shapes. The number of new photoreceptor cells was 0.2% of the number of rods in a healthy mouse retina, the journal Science reports.

But this result is also a clear progress and the "light at the end of the tunnel", which is worth focusing on in further work, experts are sure.

Ahead of the researchers are behavioral tests that will show how well the restoration of vision in animals with congenital blindness is going and what tasks they can perform after the procedure.

After a series of experiments, the same strategy can probably be applied to the treatment of retinal diseases in humans. Moreover, it is possible that other visual impairments, for example, glaucoma, will also be amenable to treatment using the new technique.

A scientific article on the results of the breakthrough work was published in the journal Nature.

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