Regenerating damaged nerve fibers in the eye

Technique to regenerate optic nerve offers hope for future glaucoma treatment.

Using gene therapy, scientists from the University of Cambridge have successfully regenerated damaged nerve fibers in the eye. This discovery could pave the way towards the development of new treatments for Glaucoma.

Scientists tested whether the gene responsible for producing a protein called Protrudin can potentially stimulate the regeneration of nerve cells and protect them from cell death after an injury.

During the study, scientists used a cell culture system to grow brain cells in a dish. They then injured their axons using a laser and analyzed the response to this injury using live-cell microscopy. They noticed that increasing the amount or activity of Protrudin in these nerve cells vastly increased their ability to regenerate.

The retinal ganglion cells in the retina extend their axons from the eye to the brain through the optic nerve to relay and process visual information. To investigate whether Protrudin might stimulate repair in the injured CNS in an intact organism, the scientists used a gene therapy technique to increase the amount and activity of Protrudin in the eye and optic nerve.

After measuring the amount of regeneration a few weeks later, scientists found that Protrudin had enabled the axons to regenerate over large distances. They also found that the retinal ganglion cells were protected from cell death.

It means this technique could protect against Glaucoma, a common eye condition.

To demonstrate Protrudin’s protective effect against Glaucoma, scientists used a whole retina from a mouse eye and grew it in a cell-culture dish. Usually, around a portion of retinal neurons die within three days of retinal evacuation; however, the scientists found that increasing or initiating Protrudin prompted practically complete protection of retinal neurons.

Dr. Veselina Petrova, from the Department of Clinical Neurosciences at the University of Cambridge, the study’s first author, said: “Glaucoma is one of the leading causes of blindness worldwide. The causes of Glaucoma are not entirely understood, but there is currently a large focus on identifying new treatments by preventing nerve cells in the retina from dying and trying to repair vision loss through the regeneration of diseased axons through the optic nerve.”

“Our strategy relies on using gene therapy – an approach already in clinical use – to deliver Protrudin into the eye. It’s possible our treatment could be further developed as a way of protecting retinal neurons from death, as well as stimulating their axons to regrow. It’s important to point out that these findings would need further research to see if they could be developed into effective treatments for humans.”

Protrudin regularly lives inside the endoplasmic reticulum, tiny structures within our cells. In this investigation, the group indicated that the endoplasmic reticulum found in axons seems to provide materials and other cell structures significant for growth and survival to help the process of regeneration after injury. Protrudin stimulates the transport of these materials to the site of injury.

Dr. Petrova added: “Nerve cells in the central nervous system lose the ability to regenerate their axons as they mature, so have minimal capacity for regrowth. This means that injuries to the brain, spinal cord, and optic nerve have life-altering consequences.”

“The optic nerve injury model is often used to investigate new treatments for stimulating CNS axon regeneration, and treatments identified this way often show promise in the injured spinal cord. It’s possible that increased or activated Protrudin might be used to boost regeneration in the injured spinal cord.”

Journal Reference:
  1. Petrova, V., Pearson, C.S., Ching, J. et al. Protrudin functions from the endoplasmic reticulum to support axon regeneration in the adult CNS. Nat Commun 11, 5614 (2020). DOI: 10.1038/s41467-020-19436-y

TRENDING

EXPLORE MORE

See stories of the future in your inbox every morning.

New Inventions