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Cells in the retina of mice can be coaxed to create new neurons following an injury, according to new research from the University of Washington. This is the most definitive demonstration to date that such regeneration is possible, given the right cues, for a specific type of neuron in the inner retina of a mammal.

If researchers could spur the development of different types of new neurons in the living human eye, they might be able to replace cells that are lost in diseases like macular degeneration and retinitis pigmentosa. Few or no treatment options are currently available for patients with these diseases.

“This is an excellent, clear demonstration that you can regrow cells of the inner retina,” says Stephen Rose, chief research officer at the nonprofit Foundation Fighting Blindness.

The retina, which is located in the back of the eye, has an outer layer of cells that detect light and translate it into electrical signals. It also has inner layers, which process the signals and send them to the brain.

In degenerative disorders like macular degeneration and retinitis pigmentosa, outer-layer cells, called photoreceptors, break down in the early stages of disease, leading to loss of vision. Extensive research has focused on replacing these cells, in an effort to restore sight. In people with advanced disease or blindness, however, the inner cell layers may also break down or become disorganized and need to be rebuilt, says Rose.

“The outer retina is like the CPU, and the inner retina is like the motherboard,” he says. “If I attach a new CPU to a dead motherboard, it won’t do any good, no matter how great a CPU it is.”

In the current work, developmental biologist Thomas Reh and his team first damaged the mice’s retinas, using a chemical known to destroy inner retinal cells. Then they injected a cocktail of proteins called growth factors. This process spurred some cells, called muller glia, to return to an immature state. Muller glia normally provide nutrition to other neurons and do not divide. Following chemical treatment, however, some of them returned to an undifferentiated state in which they resembled progenitor cells.

The immature cells then started to proliferate, some of them differentiating into mature neurons. In particular, they formed amacrine cells, which are located in the inner retina. These cells mediate electrical signals coming from the photoreceptors and are particularly important to motion detection and night vision, says Reh.

“We did not get a large number of new neurons,” he adds. “But we showed that we could make new amacrine cells, the cell type that had been lost to damage.” The findings were published this week in the online edition of the Proceedings of the National Academy of Sciences.

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Credit: Thomas Reh

Tagged: Biomedicine, stem cells, retina, macular degeneration, retinitis pigmentosa, regeneration

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