14 July 2016

Optic nerves can regenerate

Scientists partially restored vision to mice with optic nerve damage

Oleg Lischuk, N+1

American scientists managed to partially restore the vision of mice after damage to the optic nerve. The results of the work are published in the journal Nature Neuroscience (Lim et al., Neural activity promotes long-distance, target-specific regeneration of adult retinal axons).

Employees of the University of California at San Diego, the University of Utah, Harvard and Stanford Universities caused injury by clamping the optic nerve of one eye of experimental mice. Staining of retinal ganglion cells (GCS), transmitting information from photosensitive cells to the brain, showed that almost all of their axons, which are fibers of the optic nerve, reach only to the site of damage. In the absence of therapeutic effects (control group), most of the GCS died within three weeks, which caused irreversible blindness.

In the experimental group, retinal cells were stimulated daily after surgery with high-contrast moving images (for example, alternating black and white stripes). Three weeks later, they showed signs of axon regeneration, but only a short distance from the injury site.

Mice from the other group were injected with a viral vector carrying the protein cRheb1 into the eye before damage to the optic nerve. This protein stimulates the signaling pathway of the mammalian target rapamycin (mTOR), the most important regulator of cell growth. This caused an even more pronounced regeneration of the GCS axons than with visual stimulation, but they also did not reach the brain.

At the next stage of the experiment, the scientists combined the activation of mTOR in the GCS and visual stimulation. To enhance the effect, the mice temporarily sewed up the eyelids of a healthy eye. This combined effect led to the growth of axons along the entire length of the optic nerve, through the visual intersection to the primary optical nuclei of the brain (hypothalamic suprachiasmatic nucleus, ventral and dorsal lateral cranial nuclei of the thalamus), the nuclei of the midbrain (olive pretectal and posterior borderline) and additional optical targets of the brainstem (for example, medial terminal nucleus).

axons.jpg

Axons growing to the right of the optic nerve injury site are colored purple and green. A snapshot from the NIH press release Use it or lose it: Visual activity regenerates neural connections between eye and brain - VM.

Also, the axons of the GCS were found in the subcortical areas of the visual analyzer farther from the eye, in particular, in the upper hillock of the quadrilateral. Importantly, outside the visual centers, the growth of these axons was not observed, that is, they unmistakably found their way into the brain. Nevertheless, the regeneration of nerve fibers was not shown for all subtypes of GCS (about 30 of them are known in total).

Subsequent behavioral tests showed that vision in the eyes with a damaged optic nerve partially recovered after experimental treatment: the mice reacted to contrasting and moving objects (tests for the optokinetic reflex and avoidance of an impending threat), but their pupil response to light and deep vision did not recover. Thus, the therapy restored the connections of the GCS not with all departments of the visual analyzer.

Currently, researchers continue to improve the developed methodology.

Portal "Eternal youth" http://vechnayamolodost.ru  14.07.2016

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