Fish-Like Genetic Program Transforms Human Retinal Cells into Neurons

Loss of neurons in the retina caused by trauma or disease results in vision impairment or blindness, an irreversible process in humans. Notably, certain animals, such as fish, possess an inherent capability to regenerate retinal neurons by transforming another retinal cell type known as "Muller glia" into neurons.

Spontaneous conversion of this kind does not occur in humans and other mammals. However, recent research by Thomas Reh, Juliette Wohlschlegel, and colleagues at the University of Washington, U.S., published in the journal Stem Cell Reports, demonstrates that human Muller glia can be induced to change identity in a laboratory setting. This discovery holds the potential to be a source of new neurons for treating vision loss.

"Overall, our study provides a proof-of-principle that human glia can be reprogrammed to cells that are capable of making new neurons," said Thomas Reh, Ph.D., University of Washington. "This opens up an entirely new way to repair the retina in people that have lost neurons to disease or trauma."

Muller glia, supportive cells in the retina, play a crucial role in aiding the proper functioning of photoreceptors and other retinal neurons. In certain species such as fish and birds, Muller glia transform into immature retinal cells following injury, leading to the subsequent generation of new retinal neurons.

In contrast, Muller glia in the mammalian retina respond to injury by forming scars and inducing inflammation, without generating new neurons. This variation in behavior stems from the activation of distinct genetic programs in fish compared to mammalian Muller glia following injury.

Previous research has demonstrated that the artificial activation of a fish-like genetic program can transform mouse Muller glia into retinal neurons. However, it remained uncertain whether the same approach could be applied to convert human Muller glia into neurons until now.

To answer this question, the researchers conducted genetic modifications on human Muller glia in the laboratory to activate neuron-specific genetic programs, mirroring the natural process observed in fish. Remarkably, within a week, the genetically modified cells exhibited characteristics akin to immature retinal neurons.

The findings suggest that human Muller glia can be induced to transform into neurons, potentially offering a source for generating new neurons in patients' retinas in the future. It's important to mention that the Muller glia used in this study were derived from immature Muller glia. Whether similar methods can effectively convert adult human Muller glia into neurons and the extent of this transformation efficiency are aspects that still need exploration.

Reference

ASCL1 induces neurogenesis in human Muller glia., Stem Cell Reports (2023). DOI: 10.1016/j.stemcr.2023.10.021. www.cell.com/stem-cell-reports … 2213-6711(23)00423-X