Scientists have long known that the mammalian central nervous system (CNS) has a limited capacity to regenerate. But in a new study, researchers from Stanford University have shown that combining visual stimulation and chemical activation of the mammalian target of rapamycin (mTOR) led retinal ganglion cells in blind mice to regenerate, restoring partial vision. Further, the regenerated axons reconnected to their correct targets in the brain, the researchers reported today (July 11) in Nature Neuroscience.
This approach “offers a lot of hope, because it’s really the best regeneration anybody’s seen,” biologist Thomas Reh of the University of Washington in Seattle, who was not involved in the work, told The Scientist. “But it’s still just a small number of axons regenerating . . . and the amount of vision restored is not nearly what we would like to see” in humans, he added.
Unlike the peripheral nervous system, the brains and spinal cords of mammals do not readily regenerate after injury. Secretion of proteins from myelin, buildup of scar tissue, and reduced production of growth factors are all thought to play a role in preventing regrowth of axons in the CNS. Scientists had previously succeeded in partially regenerating murine retinal axons by stimulating growth factors such as mTOR and cyclic adenosine monophosphate (cAMP), or removing growth inhibitors such as Kruppel-like factor 4 (KLF4). However, the regenerated retinal nerves did not regrow the full length of the optic nerve and reconnected to the wrong targets.
“We’ve known for 100 years or more that neurons in the CNS don’t regenerate after injury,” study coauthor Andrew Huberman, of Stanford, told The Scientist. Still today, he added, “the best treatment for spinal cord injury is the wheelchair, and the best treatment for eye injury is the seeing-eye dog.”