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Longevity Briefs: Gene therapy rejuvenates damaged brain cells, restoring sight

Posted on 8 December 2020

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Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: In development, brain cells show some regenerative capabilities allowing them to adapt to change and even recover from injury. These abilities have been shown to diminish as we get older.

Although retinal ganglion cells (RGCs) are located within the eyes, they are brain cells, connecting the rod and cone cells of our eyes to our optic nerve. If these cells are damaged once they have matured, they are unable to regenerate and the sight of the individual is lost.

Source: Encyclopedia Britannica

What did the researchers do: In a groundbreaking study, researchers tested the ability of RGCs to regenerate if the optic nerve was crushed. The team stimulated the rejuvenation of the RGCs’ by infecting them with a harmless viral vector which had been genetically engineered to trigger the expression of three of the four Yamanaka factors – Oct4, Sox2 and Klf4 (OSK). Yamanaka factors are molecular messengers that drive the cell back from a fully differentiated somatic cell, to a pluripotent stem cell, with the ability to re-differentiate back into a healthy body cell.

Key takeaway(s) from this research: The results showed that the over-expression of the OSK factors caused regeneration of the RGCs, reversing the damage caused by the crushing of the optic nerve. Importantly, this was not only the case in young mice, which already have some regenerative ability, but also in older mice.

Restoring vision in mice. Retinal ganglion cells (RGCs) transmit visual information from the eye to the brain along projections called axons. Damage to the RGC axons prevents transmission of this information, leading to sight loss. Lu et al.2 report that treatment of damaged RGCs with a transcription-factor cocktail called OSK restores the cells to a youthful state, leading to axon regeneration and restoration of sight in mice. Source: Nature

These findings could provide the framework for repairing aged or damaged human brains in the not-so-distant future.

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