Gene therapy to regenerate the optic nerve may offer new glaucoma treatments

Researchers find that gene therapy can be used to regenerate damaged axons in the eye and help develop new treatments for glaucoma, one of the leading causes of blindness worldwide. Did.

In one study, “Protorzine functions from the endoplasmic reticulum and supports axonal regeneration in the adult central nervous system.Was announced in Nature CommunicationsScientists have tested whether genes involved in the production of the protein protordine can stimulate nerve cell regeneration and protect them from cell death after injury.

“Axon damage has lasting consequences because adult axons of the mammalian central nervous system are inherently incapable of regeneration. One approach to enhancing regeneration is growth molecules and cell organs. This is achieved by expressing the adapter molecule protordine, which is usually found at low levels in non-regenerating neurons, “the researchers write.

“Elevated protordin expression allowed strong central nervous system regeneration both in vitro in primary cortical neurons and in vivo injured adult optic nerve. Overexpression of protordin allowed vesicles in the distal axons, integrin. , And promoted the accumulation of Rab11 endosomes and eliminated the follicular localization of protordin, the kinesin-binding or phosphoinositide-binding properties abolished the regenerative effect.

“These results establish that protorzine promotes regeneration by acting as a scaffold that connects axonal organelles, motors, and membranes, and plays an important role in these cellular components that mediate the regeneration of the adult central nervous system. Indicates to do. “

The team used a cell culture system to grow brain cells in a dish. The axons were then damaged using a laser and the response to this damage was analyzed using a living cell microscope. Researchers have found that increasing the amount or activity of protordin in these nerve cells significantly increases their ability to regenerate.

Retinal ganglion cells extend axons from the eye to the brain through the optic nerve to relay and process visual information. To investigate whether protordin stimulates the repair of the injured central nervous system in intact organisms, scientists have relied on gene therapy techniques to increase the amount and activity of protordin in the eye and optic nerve. ..

When they measured the amount of regeneration weeks after the crush injury to the optic nerve, the team discovered that Protordin allowed axons to regenerate over long distances. They also found that retinal ganglion cells were protected from cell death.

Researchers have shown that this technique may help protect against glaucoma, a common eye condition. In glaucoma, the optic nerve that connects the eye to the brain is gradually damaged, often increasing pressure in the eye.

If not diagnosed early enough, glaucoma can lead to loss of vision. In the UK, 1 in 50 people over the age of 40 and 1 in 10 people over the age of 75 are affected by glaucoma.

To demonstrate this protective effect of protorzine on glaucoma, researchers used the entire retina from the mouse eye and grew it in a cell culture dish. Normally, about half of retinal neurons die within 3 days of retinal removal, but scientists have found that increased or activated protordin leads to near-complete protection of retinal neurons.

“The cause of glaucoma is not fully understood, but it is now possible to prevent the death of nerve cells in the retina and try to repair vision loss by regenerating diseased axons through the optic nerve. There is a great deal of focus on identifying new treatments, said Dr. Veselina Petrova of the Department of Clinical Neuroscience at Cambridge University, the lead author of the study.

“Our potential [gene therapy] Treatment can be further developed as a way to protect retinal neurons from death and as a way to stimulate and re-grow their axons. It is important to point out that these findings will require further research to see if they can develop into effective treatments for humans. “

Protorzine is usually present in the endoplasmic reticulum. In this study, the team showed that the endoplasmic reticulum found in axons appears to provide important materials and other cellular structures for growth and survival to support the post-injury regeneration process. .. Protorzine stimulates the transport of these substances to the site of injury.

“Nerve cells in the central nervous system lose the ability to regenerate axons as they mature, so their ability to regenerate is very limited. This has life-changing consequences for brain, spinal cord, and optic nerve damage. That means, “Petrois continued. “The optic nerve injury model is often used to investigate new therapies for stimulating CNS axonal regeneration, and the therapies identified in this way are often promising in the injured spinal cord. Or activated protorzine may be used to promote regeneration of the injured spinal cord. “