By Jacky Moore
Led by associate professor of neurobiology Andrew Huberman, researchers from Stanford, Harvard and University of California, San Diego have partially restored blindness in mice. Huberman intends to apply the results of this study toward repairing damaged eyesight in humans.
The study used mice that were intentionally blinded in one eye through damage to the optic nerve, which links the retina to the brain. The rodents were divided into three treatment groups, and each group received gene therapy, visual stimulation or both.
The researchers specifically experimented on neurons called retinal ganglion cells, which are located in the innermost layer of the retina. These cells send visual information in the form of electrical impulses, called action potentials, from the eye to the brain via axons. Axons, which are often compared to telegraph wires, are the long, thin components of neural cells that form synaptic connections with different parts of the brain. An eye’s retinal ganglion cells’ axons collectively make up the eye’s optic nerve.
“Retinal ganglion cells have one specific job,” Huberman said. “It’s the only job they perform, and that job is to take visual information as seen by the eye and convey it to the brain.”
In mice that received both gene therapy and visual stimulation, some damaged retinal ganglion cells regenerated completely, allowing the rodents to see large moving objects. To the relief of the researchers, each regenerated axon also connected to its correct target in the brain.
“This is extremely reassuring because what it suggests is that in humans, if we were to stimulate regeneration of a given set of neurons after an injury, those neurons would have the wisdom to wire up to their targets in the brain in the right way,” Huberman said. “The neurons know exactly who they are, and they find their way home.”
The mice study was designed to answer two important neurobiological questions that, when solved, could allow scientists to regenerate cells not just for vision but also elsewhere in the central nervous system.
“The first question was ‘How could we get neurons to regenerate?’” Huberman said. “The second question was ‘If they do regenerate, do they form correct patterns of connection?’”
In one set of mice, a gene therapy was introduced to each rodent’s injured eye in the form of a virus expressing mTOR, or mammalian target of rapamycin. mTOR, a gene relating to cell growth, activated growth of the mice’s retinal ganglion cells. The researchers found that retinal ganglion cells exposed to elevated levels of mTOR regenerated a short distance but were unable to reach the brain.
Another group of partially blind mice was placed in an “IMAX for mice,” where the creatures viewed high-contrast movies of drifting gradients and moving black and white bars that electrically activated neural growth. Unfortunately, the retinal ganglion cells of mice who watched movies regenerated even less than those of the mice who received gene therapy.
However, when visual stimulation and gene therapy worked synergistically, the axons of the mice’s retinal ganglion cells grew very long distances in short periods of time and were able to reach the brain. The neural connections formed in the optic nerves of the rodents in this group allowed said mice to respond appropriately to moving objects: The mice ran away from perceived threats.
However, the mice’s restored eyesight was by no means perfect. Only 1 to 5 percent of the total retinal ganglion cell population regenerated, which allowed for only very limited vision. Additionally, due to temporal and financial restraints, the researchers are unsure if all types of retinal ganglion cells will connect correctly to their targets in the brain during neural regeneration.
Even so, Huberman is unfazed and looks forward to building on the results of the study.
“I have every reason to believe that these audacious goals are going to be met not just because of the work that my lab is doing, but because of the work that other labs [besides my own] at Stanford and other laboratories in the United States are doing,” Huberman said.
Contact Jacky Moore at jackymoore99 ‘at’ gmail.com.