中枢神经系统,视网膜神经节细胞 z-bo 2020-09-23 357

　　Scientists have long known that the regenerative capacity of the mammalian central nervous system (CNS) is limited. But in a new study, researchers from Stanford University demonstrated that combining visual stimulation with chemical activation of mammalian target of rapamycin (mTOR) can regenerate retinal ganglion cells in blind mice. So as to restore some vision.

　　Thomas Reh, a biologist at the University of Washington, was not involved in this work, but he told The Scientist this way: "This method offers great hope. Although it only regenerates a small part of axons, the amount of vision restoration is almost We have never achieved it in humans." Extended reading: Chinese female scholars use CRISPR technology to improve hereditary blindness; Science focuses on breakthrough results: let blind mice move freely; American scientists have developed miniature retinas to bring hope to blind patients.

　　Different from the peripheral nervous system, the brain and spinal cord of mammals are not easy to regenerate after injury. Protein secreted from myelin, accumulation of scar tissue, and decreased production of growth factors are all thought to prevent axon regeneration in the central nervous system. Scientists have successfully partially regenerated mouse retinal axons by stimulating growth factors such as mTOR and cyclic adenosine monophosphate (cAMP), or removing growth inhibitory factors such as Kruppel-like factor 4 (KLF4). However, the regenerated retinal nerve could not regrow the entire length of the optic nerve and reconnected to the wrong target.

　　The co-author of this article, Andrew Huberman of Stanford University, told The Scientist: "For more than 100 years, we have known that the neurons of the central nervous system cannot regenerate after injury. Spinal cord injury patients can only rely on wheelchairs, while eye trauma patients have Can rely on guide dogs."

　　In the current study, Huberman and his colleagues destroyed the optic nerve of mice and labeled the animal’s retinal ganglion cells (RGC) with fluorescent dyes. The researchers then exposed the blind mice to high-contrast visual stimuli—including moving light bars on the screen every day for three weeks. The other group of control mice were not exposed to this stimulus.

　　Huberman's team injected a virus that highly expresses the Rheb1 protein into one eye of another group of mice to activate the growth-promoting protein mTOR. Two weeks later, the researchers destroyed the optic nerves of rodents. Three weeks later, the researchers tagged the cells to measure the degree of nerve regeneration. The mice in the control group did not receive injections, or received injections of saline or control virus.

　　Finally, Huberman and his colleagues exposed another group of mice to mTOR treatment and visual stimulation. The researchers sutured the non-injured eyes of the mouse to encourage it to use the injured eyes.

　　In mice exposed only to visual stimuli, RGC axons re-growth a short distance across the injury site, but did not extend the entire length of the optic nerve to the brain. Mice treated with mTOR also showed similar partial axonal regeneration. But the researchers found that in mice that received visual stimulation and mTOR treatment with one eye closed, axon regeneration was significantly longer than in mice that received either treatment. In 70% of mice, axons regenerate to the optic chiasm.

　　Huberman’s team observed that these nerves are also connected to the correct target in the brain. He said: "Before this study, we didn't know whether the regenerated neurons would linger in the brain."

　　Researchers report that mice receiving dual treatments can obtain limited vision. Huberman said: "This is equivalent to a completely blind person now being able to walk through a room and avoid large objects."

　　The team is now testing the use of visual stimuli and virtual reality in humans. Huberman and his colleagues currently do not plan to try mTOR treatment in humans because it is a high-risk and more invasive procedure.

　　Marco Zarbin, a professor of ophthalmology at Rutgers University’s New Jersey School of Medicine, was not involved in the study, but he pointed out: “This study provides great hope for the treatment of patients with optic nerve trauma. However, we must do more to make These findings in animal models of human diseases are translated into the treatment of blind human patients with optic nerve degeneration."

　　In Zarbin's view, the main limiting factors of this study include: the relatively small number of regenerated axons, not all visual function recovery, and the general applicability of the optic nerve injury model.

　　At the same time, Huberman is optimistic that in humans, retinal regeneration is within reach. He said: "In the next one to five years, I think we will see this problem resolved."