Researchers Unlock Regenerative Potential of Cells in Mouse Retina

Cells within an injured mouse eye can be coaxed into regenerating neurons and those new neurons appear to integrate themselves into the eye’s circuitry, new research shows. The findings potentially open the door to new treatments for eye trauma and retinal disease. The study appeared in the July 26 issue of Nature and was funded in part by NEI.

“The findings are significant because they suggest the feasibility of a novel approach for encouraging regeneration in the mammalian retina, the light sensitive tissue at the back of the eye that dies in many blinding diseases,” said Dr. Tom Greenwell, program director at NEI. “Importantly, the investigation also demonstrates that newly generated cells in the mouse retina not only look and behave like neurons, they also wire correctly to the existing neural circuitry at the back of the eye.”

The study looked to the zebrafish for clues about how to encourage regeneration in the mouse eye. When a zebrafish injures its eye, cells within the eye naturally regenerate, allowing the fish to maintain vision. Mammals lack this regenerative ability.

In studying zebrafish, the research team homed in on Müller glia, a type of retinal cell that supports the health and functioning of neighboring neurons and that also exhibits an innate regenerative ability. Sometimes referred to as the stem cells of the zebrafish eye, Müller glia are the cells from which all other types of retinal cells are regenerated in the fish.

“We’re showing for the first time that Müller glia in the adult mouse can give rise to new neurons after injury, and these neurons have the gene expression pattern, the morphology, the electrophysiology and the epigenetic program to look like interneurons instead of glia,” one of the researchers said.

The studied cells had formed functioning synapses—connections from one neuron to another—and responded to light in a way that’s typical of a type of interneuron. The cells had also integrated with retinal cells that convey signals to the brain.

The findings suggest that the regenerated cells were making synapses and integrating into both sides of the circuitry, presynaptically and postsynaptically. This approach could be useful for treatment of acute eye injuries and central retinal arterial occlusion—a stroke of the eye. The next step is to boost Müller glia numbers, researchers said.