Mice with human cones

Human cells restored mice's vision

Kirill Stasevich, Science and Life (nkj.ru ), based on materials The Scientist.

One of the most common causes of blindness in the elderly is age–related macular degeneration of the retina. The macula, or yellow spot, is called the zone of greatest visual acuity. It is thanks to the visual receptors of the macula that we can read, drive a car and generally do any job where we need to notice even the smallest details. As you can understand from the name, with age-related macular degeneration, just the photoreceptors of the macula die, and most often the cones, thanks to which we distinguish colors. But what if we try to replace the dead photoreceptors with new ones grown from stem cells?

Experiments by researchers from King's College London demonstrate that transplanted healthy cones may well restore vision to eyes with a diseased retina. Experiments were conducted on mice predisposed to retinal degeneration, but the receptors for transplantation were grown from human cells. In one case, these were embryonic stem cells, from which normal, healthy cones were obtained. In another case, stem cells were obtained from mature, differentiated cells taken from a person with congenital achromatopsia – the so-called complete inability to distinguish colors. Achromatopsia occurs due to non-functioning cones: they are in the retina, but they do not react to light.

Mature human cells were reprogrammed into a stem state using a special cocktail of signaling proteins – induced stem cells were obtained. They, like ordinary embryonic stem cells, could be turned into any other type of cell – for example, cones. The genetic defect that caused achromatopsia in the donor was present in all the cells of the body, so the cones, which after all the manipulations turned out to be induced stem cells, also did not feel the light.

Human cones were transplanted into mice whose immunity was specifically suppressed so that their body would not reject foreign cells. Some mice were transplanted with normal cones, some with defective ones, some received cones only in one eye, some in both. An article in Cell Reports (Ribeiro et al., Restoration of visual function in advanced disease after transplantation of purified human pluripotent stem cell-derived cone photoreceptors) states that human receptors were normally embedded in the retina and formed all the necessary intercellular connections to transmit information about what they saw. However, defective cones could not transmit anything, but normal cones worked. This was seen both with the help of special tests that allowed us to see the activity of neurons in the retina, and by the behavior of mice. Those of them to whom normal receptors were transplanted began to distinguish the difference in illumination and tried to hide in a less illuminated place – as mice should.

Attempts to treat the degenerating retina with the latest biotechnological methods have been made for a long time. Three years ago, we wrote about how two elderly people managed to partially regain their eyesight – they were transplanted healthy retinal cells. However, in that work, not photoreceptors were transplanted, but auxiliary feeding cells that help rods and cones to live and work. Retinal dystrophy often begins with the death of feeding cells, followed by the death of receptors. But if you transplant not only them, but also the receptors themselves, it will help to restore vision to a greater extent, or at least slow down progressive blindness.

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