Researchers Coax Retinal Muller Glia Cells to Become Regenerating Neurons that Function

September 1, 2017: By Joan McKenna

1 Ophthalmic NewsResearchers have coaxed retinal Müller glia cells in an injured mouse eye to become regenerating neurons that become part of the eye’s circuitry, according to a study published July 26 in Nature.

The study, by Tom Reh, PhD, and his team at the UW Medicine in Seattle, was funded in part by the National Eye Institute.

Müller glia cells are retinal cells that support the health and functioning of neighboring neurons and also exhibit regenerative ability.

Earlier work by the team showed that activating a transcription factor called Ascl1 in newborn mice could direct Müller glia to become retinal neurons that activated genes involved in regeneration. However, in older mice, those genes became inaccessible.

Using the anti-cancer agent trichostatin A (TSA) made the genes accessible again, the scientists found.

For this study, the team used an adult mouse model genetically engineered to express Ascl1 in Müller glia in response to tamoxifen, a commonly used breast cancer drug.

They injected the mice with TSA and tamoxifen. Over the next several weeks, the shape and behavior of the cells showed evidence of regeneration.

About two weeks following injury, the cells responded to light as if they were interneurons, retinal cells that transmit signals from photoreceptors to the brain.

The cells also formed functioning synapses, or connections from one neuron to another, and had integrated with retinal cells that convey signals to the brain.

Reh said the approach could be useful for treatment of acute eye injuries and central retinal arterial occlusion. Reh’s lab is investigating other types of regenerative strategies to address all the retinal cell types.

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