Aging limits neuron regeneration in the mouse retina

Inside an aging mouse retina, the cells that support and nourish neurons struggle to change identity. Levi Todd's lab at Upstate Medical University found that retinal glia can still be reprogrammed into neurons in aged tissue, but the process is far less efficient than in young animals. The paper was published in the Proceedings of the National Academy of Sciences.

The idea rests on a natural repair mechanism. In animals including zebrafish and frogs, glial cells can detect the loss of neurons, return to a stem-cell-like state and generate replacements. Research in the past decade showed that researchers could trigger a similar process in the retinas of young mice. The field expanded after a 2017 discovery that new retinal neurons could be generated from glia, but studies largely stayed on young animals.

Aging appears to close that door in two ways. Neurons and glia present from birth can become less flexible over time, unlike skin or liver cells that constantly turn over. At the same time, inflammation rises with age. The blood-brain barrier — which normally keeps the immune system away from nervous tissue — also weakens, exposing the brain and retina to an environment that makes regeneration more difficult.

Todd's team found a partial way through the block: anti-inflammatory steroids partly restored the retina's regenerative response in aged tissue. That result points toward a more precise strategy, but it is not a finished treatment. The lab now plans to identify the molecules and pathways involved and examine whether monoclonal antibodies could target them without the negative side effects that can come with broad immune suppression.

Because this result comes from mouse retinas, it does not yet show that people can regrow lost neurons.