New Research: Neuroscientists Regenerate Damaged Optic Nerves in Mice, May Lead to Future Treatment for Glaucoma or Other Optic Nerve Disorders

a laboratory mouse

A group of United States-based neuroscience researchers has used a combination of gene therapy and visual stimulation to create a partial regeneration of damaged optic nerves in blind laboratory mice. Although this research is in its earliest stages and has been performed only with mice, the researchers are “cautiously optimistic” that these findings could one day be used to treat adult patients with vision loss caused by problems with the eye-brain connection – the optic nerve – such as glaucoma.

Please note: Although this regenerative cell research has produced interesting results in mice thus far, it must be subjected to additional, longer-term, rigorous study and human clinical trials, encompassing many more years of research.

This new optic nerve regeneration research, entitled Neural activity promotes long-distance, target-specific regeneration of adult retinal axons, has been published in the August 2016 issue of Nature Neuroscience, a monthly scientific journal that positions itself as “the voice of the worldwide neuroscience community.” Nature Neuroscience publishes original, peer-reviewed research relating specifically to neuroscience, with priority given to studies that provide insights into the functioning of the nervous system (which includes the optic nerve and the visual system).

The authors are Jung-Hwan A. Lim; Benjamin K. Stafford; Phong L. Nguyen; Brian V. Lien; Chen Wang; Katherine Zukor; Zhigang He; and Andrew D. Huberman, who represent the following institutions: the University of California, San Diego, La Jolla, CA; Harvard Medical School, Boston, MA; Utah State University, Logan, UT; and Stanford University School of Medicine, Stanford, CA.

Some Terminology Used in the Research

Here is a brief explanation of some key terms that are used in this regenerative cell research:

  • Ganglion cells: Nerve cells that are found in the retina. They are located near the inner surface of the retina and give rise to optic nerve fibers (axons) that transmit information from the retina to several regions in the brain.
  • Axons: Long, thin fibers contained within ganglion cells. They extend down the optic nerve in a bundle and then branch out to different regions of the brain, where they connect with other nerve cells to interpret visual information.
  • mTOR: The mammalian target of rapamycin. Rapamycin is a compound produced by bacteria that can suppress or prevent the immune response and has anti-tumor properties. According to Scientific American, “while many factors are responsible for adult brain cells’ lack of regenerative capacity, one well-studied cause is the winding down, over time, of a growth-enhancing cascade of molecular interactions, known as the mTOR pathway, within these cells.” In this case, the researchers used genetic intervention to activate, or “switch on,” the regenerative mTOR pathway once again.

About the Optic Nerve Research

Edited and excerpted from First-ever restoration of vision achieved in mice, via MedicalXpress:

In experiments in mice, the scientists coaxed optic-nerve cables, responsible for conveying visual information from the eye to the brain, into regenerating after they had been completely severed, and found that they could retrace their former routes and re-establish connections with the appropriate parts of the brain. That unprecedented, if partial, restoration could pave the way to future work that enables blind people to see. The animals’ condition prior to the scientists’ efforts to regrow the eye-to brain-connections resembled glaucoma.

In the study, adult mice in which the optic nerve in one eye had been severed were treated with either a regimen of intensive daily exposure to high-contrast visual stimulation, in the form of constant images of a moving black-and-white grid, or biochemical manipulations that kicked the mTOR pathway (explained above) within their retinal ganglion cells back into high gear, or both.

The mice were tested three weeks later for their ability to respond to certain visual stimuli, and their brains were examined to see if any axonal regrowth had occurred.

While either visual stimulation or mTOR-pathway reactivation produced some modest axonal regrowth from retinal ganglion cells in mice’s damaged eye, … when the two approaches were combined—and if the mouse’s undamaged eye was temporarily obstructed in order to encourage active use of the damaged eye—substantial numbers of axons grew … and migrated to their appropriate destinations in the brain.

“Somehow these retinal ganglion cells’ axons retained their own GPS systems,” [study author] Huberman said. “They went to the right places, and they did not go to the wrong places.” In other words, the regenerating axons, having grown back to diverse brain structures, had established functional links with these targets. The mice’s once-blind eye could now see.

However, even mice whose behavior showed restored vision on some tests, failed other tests that probably required finer visual discrimination, said Huberman. Further progress, he suggested, will depend on boosting total numbers of retinal ganglion cell axons that successfully extend back to, and establish former contact with, their target structures.”

More about Glaucoma

The term “glaucoma” describes a group of eye diseases that can lead to blindness by damaging the optic nerve. It is one of the leading causes of vision loss and blindness. The human eye continuously produces a fluid, called the aqueous, that must drain from the eye to maintain healthy eye pressure.

Types of Glaucoma

In primary open-angle glaucoma, the most common type of glaucoma, the eye’s drainage canals become blocked, and the fluid accumulation causes pressure to build within the eye. This increasing pressure can cause damage to the optic nerve, which transmits information from the eye to the brain. Vision loss is usually gradual and often there are no early warning signs.

In angle-closure glaucoma, also called “acute” glaucoma, the aqueous cannot drain properly because the entrance to the drainage canal is either too narrow or is closed completely. In this case, eye pressure can rise very quickly and cause an acute glaucoma attack. Symptoms can include sudden eye pain, nausea, headaches, and blurred vision. Acute glaucoma is a true ocular emergency and requires immediate treatment.

In normal-tension glaucoma, also called low-tension/low pressure glaucoma, individuals with the disease experience optic nerve damage and subsequent vision loss, despite having normal intraocular [i.e., within the eye] pressure (IOP).

Most eye care professionals define the range of normal IOP as between 10 and 21 mm Hg [i.e., millimeters of mercury, which is a pressure measurement]. Most persons with glaucoma have an IOP measurement of greater than 21 mm Hg; persons with normal-tension glaucoma, however, have an IOP measurement within the normal range.

Visual Field Loss

Glaucoma results in peripheral (or side) vision loss initially, and the effect as this field loss progresses is like looking through a tube or into a narrow tunnel. This constricted “tunnel vision” effect makes it difficult to walk without bumping into objects that are off to the side, near the head, or at foot level.

A living room viewed through a constricted visual field

A living room viewed through a constricted visual field.
Source: Making Life More Livable. Used with permission.

Glaucoma is an especially dangerous eye condition because most people do not experience any symptoms or early warning signs at the onset. Glaucoma can be treated, but it is not curable. At present, the damage to the optic nerve from glaucoma cannot be reversed.

You can learn more about the different treatments for glaucoma, including laser peripheral iridotomy (LPI), selective laser trabeculoplasty (SLT), and eye drops to lower eye pressure, on the VisionAware website.

More about the Study from Nature Neuroscience

From the study summary and abstract:

Axons in the mammalian [i.e., mammal, including mice] central nervous system (CNS) fail to regenerate after injury. Here we show that if the activity of mouse retinal ganglion cells (RGCs) is increased by visual stimulation or using chemogenetics [i.e., chemical-genetic interventions], their axons regenerate.

We also show that if enhancement of neural activity is combined with elevation of the cell-growth-promoting pathway involving mammalian target of rapamycin (mTOR), RGC axons regenerate long distances and re-innervate the brain.

Analysis of genetically labeled RGCs revealed that this regrowth can be target specific: RGC axons navigated back to their correct visual targets and avoided targets incorrect for their function. Moreover, these regenerated connections were successful in partially rescuing a subset of visual behaviors.

Our findings indicate that combining neural activity with activation of mTOR can serve as powerful tool for enhancing axon regeneration, and they highlight the remarkable capacity of CNS neurons to re-establish accurate circuit connections in adulthood.

More about Glaucoma at VisionAware