New treatments for glaucoma are a step closer after gene therapy was found to regenerate damaged nerve fibres in the eye, British researchers say.
A University of Cambridge study, published in the latest Nature Communications, reveals that the gene responsible for the production of Protrudin could be key.
The team, led by Dr Richard Eva, Professor Keith Martin and Professor James Fawcett from the John van Geest Centre for Brain Repair, used a cell culture system to grow brain cells in a dish and then used a laser to damage their axons.
When they analysed the response to the injury, using live-cell microscopy, they found that increasing the amount or activity of Protrudin in the nerve cells increased significantly their ability to regenerate.
The researchers used a gene therapy technique to increase the amount and activity of Protrudin in the eye and optic nerve and when they measured the amount of regeneration a few weeks after a crush injury to the optic nerve, Protrudin had enabled the axons to regenerate over large distances.
They also found that the retinal ganglion cells were protected from cell death.
The researchers demonstrated that this technique may help protect against glaucoma by using a whole retina from a mouse eye and growing it in a cell-culture dish.
About half of retinal neurons normally die within three days of retinal removal, but the research team found that increasing or activating Protrudin led to almost complete protection of retinal neurons.
Dr Veselina Petrova from the Department of Clinical Neurosciences at the University of Cambridge said: “Glaucoma is one of leading causes of blindness worldwide. The causes of glaucoma are not completely understood, but there is currently a large focus on identifying new treatments by preventing nerve cells in the retina from dying, as well as 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 is normally located within the endoplasmic reticulum and the researchers showed that the endoplasmic reticulum found in axons provides materials and other cellular structures that are important for growth and survival to support regeneration following injury.
Dr Petrova said: “Nerve cells in the central nervous system lose the ability to regenerate their axons as they mature, so have very limited 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.”
Petrova, V et al. Protrudin functions from the endoplasmic reticulum to support axon regeneration in the adult CNS. Nat Comms 5 November 2020; doi: 10.1038/s41467-020-19436-y
Leave a Reply