Scientists have used gene therapy to regenerate damaged nerve fibers in the eye, in a discovery that could help develop new treatments for glaucoma, one of the leading causes of blindness worldwide.
Axonii – nerve fibers – in the central nervous system of adults (CNS) does not normally regenerate after injury and disease, which means that the damage is often irreversible. However, there have been a number of findings in the last decade that suggest that it may be possible to stimulate regeneration.
In a study Recently published in Nature Communications, scientists tested whether the gene responsible for producing a protein known as Protrudin could stimulate nerve cell regeneration and protect them from cell death after injury.
The team, led by Dr. Richard Eva, Professor Keith Martin and Professor James Fawcett of the John van Geest Center for Brain Repair at Cambridge University, used a cell culture system to grow brain cells in a vessel. They then injured their axons using a laser and analyzed the response to this lesion using living cell microscopy.
The researchers found that increasing the amount or activity of Protrudin in these nerve cells greatly increased their ability to regenerate.
Nerve cells in the retina, known as retinal ganglion cells, extend their axons from the eye to the brain through the optic nerve to retransmit and process visual information.
The main cause of blindness is glaucoma
To investigate whether Protrudin could stimulate the repair of injured CNS in an intact organism, the researchers used a gene therapy technique to increase the amount and activity of Protrudine in the eyes and optic nerve.
When they measured the amount of regeneration a few weeks after an optic nerve injury, the team found that Protrudin allowed the axons to regenerate over long distances. They also found that the retinal ganglion cells were protected from cell death.
Thus, researchers have shown that this technique can help protect against glaucoma, a common eye condition. In glaucoma, the optic nerve that connects the eye to the brain is progressively damaged, often in association with the increased pressure inside the eye.
If not diagnosed early enough, glaucoma can lead to vision loss. In the UK, one in 50 people over the age of 40 and one in 10 people over the age of 75 are affected by glaucoma.
To demonstrate this protective effect of Protrudine against glaucoma, the researchers used an entire retina from a mouse eye and raised it in a cell culture vessel.
Usually, about half of retinal neurons die within three days of retinal removal, but the researchers found that increasing or activating Protrudine led to almost complete protection of retinal neurons.
Dr. Veselina Petrova of the Department of Clinical Neuroscience at the University of Cambridge, the first author of the study, said: “Glaucoma is one of the leading causes of blindness worldwide. The causes of glaucoma are not fully understood, but there is currently a strong emphasis on identifying new treatments to prevent retinal nerve cells from dying, as well as trying to repair vision loss by regenerating diseased axons through the optic nerve.
How the study for the treatment of glaucoma worked
“Our strategy is based on using gene therapy – an approach already in clinical use – to deliver Protrudin to the eye. It is possible that our treatment will be further developed as a way to protect retinal neurons from death, as well as to stimulate their axons to grow. It is important to emphasize that these findings would require further research to see if they could be developed into effective treatments for humans, ”the scientist added.
Protrudine normally resides in the endoplasmic reticulum, small structures in our cells. In this study, the team showed that the endoplasmic reticulum found in the axons appears to provide materials and other cellular structures important for growth and survival to support the regeneration process after injury. Protrudine stimulates the transport of these materials to the site of injury.
Dr. Petrova added: “Nerve cells in the central nervous system lose their ability to regenerate their axons as they mature, so they have a very low ability to grow. This means that injuries to the brain, spinal cord and optic nerve have life-changing consequences.
“The optic nerve injury model is often used to investigate new treatments to stimulate CNS axon regeneration, and treatments identified in this way often show promise in the injured spinal cord. Increased or activated Protrudine may be used to stimulate regeneration in the injured spine, ”she concluded.