Optical surgery has come a long way since the farmer’s wife took a carving knife to the tails of those three blind mice. In contrast to this rather rudimentary operation, scientists have now managed to regrow the damaged optic nerves of lab mice, partially restoring their vision.
Until now, it had been presumed that once destroyed, the connecting branches of nerve cells – known as axons – cannot be regenerated. However, recent research has shown that increasing the activity of a protein called mTOR can stimulate these axons to partially repair themselves – though not quite enough to reconnect to the central nervous system and restore sight.
Using this as a starting point, the study authors genetically engineered mice to produce elevated levels of mTOR in their retinal nerve cells, before crushing the optic nerve behind one of their eyes. Over the following three weeks, these mice spent much of their time in cages watching projections of moving black lines.
At the end of this period, the researchers discovered that the axons of the optic nerve had partially regrown, reaching as far as the optic chiasm, suggesting that repeated stimulation, combined with mTOR upregulation, does indeed cause some degree of axon regeneration.
In an attempt to take this a step further, the researchers then repeated the experiment but sutured shut the good eye of each mouse, forcing them to look at the moving lines with their damaged eye. Writing in the journal Nature Neuroscience, the authors reveal that this resulted in a 500-fold improvement in axon regrowth, with many of these branches extending all the way to the brain.
Perhaps more significantly, these axons were able to reconnect to their appropriate target sites in the brain while avoiding incorrect sites, suggesting they actually remember where to go when they regrow.
To test the effects of this regeneration, the researchers subjected the mice to a number of vision tests, finding that they were able to track moving objects and detect the presence of overhead objects. However, the mice did not perform so well on tests designed to evaluate their depth perception, suggesting that their optic nerves may not have regenerated quite enough to reach certain brain areas involved with this process.
Despite the fact that not all of the damaged axons were regenerated, study co-author Andrew Huberman said in a statement that those that did showed “remarkable regrowth,” and hopes to one day perfect this technique in order to create new treatments for vision impairment in humans.
Image: Regenerating optic nerve cell axons (in magenta and green), extending from the site of injury (seen on the left). Andrew D. Huberman