Fight Aging!

In what seems an important incremental advance in nerve regeneration, researchers have demonstrated regrowth of damaged portions of the optic nerve in mice, and partial vision restoration as a result. Once past the initial point of provoking regeneration of nerve tissue, the challenge here is as much to identify the degree to which vision is restored as it is to actually repair damaged nerves. Mice cannot be walked through a standard eye exam, and they cannot tell you in detail just how good or bad their vision is. Determining how well they can see after the processes of damage and regeneration is a difficult undertaking, though clearly here there is a lot of room for improvement.

In experiments in mice, scientists coaxed optic-nerve cables, responsible for conveying visual information from the eye to the brain, into regenerating after they had been completely severed, and found that they could retrace their former routes and re-establish connections with the appropriate parts of the brain. The animals' condition prior to the scientists' efforts to regrow the eye-to brain-connections resembled glaucoma, the second-leading cause of blindness. Glaucoma, caused by excessive pressure on the optic nerve, affects nearly 70 million people worldwide. Vision loss due to optic-nerve damage can also accrue from injuries, retinal detachment, and other sources.

Retinal ganglion cells are the only nerve cells connecting the eye to the brain. Damage to mammalian retinal ganglion cells' axons spells permanent vision loss. Mammalian axons located outside the central nervous system do regenerate, though. And during early development, brain and spinal cord nerve cells abundantly sprout and send forth axons that somehow find their way through a thicket of intervening brain tissue to their distant targets. While many factors are responsible for adult brain cells' lack of regenerative capacity, one well-studied cause is the winding down, over time, of a growth-enhancing cascade of molecular interactions, known as the mTOR pathway, within these cells.

In the study, adult mice in which the optic nerve in one eye had been crushed were treated with either a regimen of intensive daily exposure to high-contrast visual stimulation, in the form of constant images of a moving black-and-white grid, or biochemical manipulations that kicked the mTOR pathway within their retinal ganglion cells back into high gear, or both. The mice were tested three weeks later for their ability to respond to certain visual stimuli, and their brains were examined to see if any axonal regrowth had occurred. Importantly, while retinal ganglion cells' axons in the crushed optic nerve had been obliterated, the front-line photoreceptor cells and those cells' connections to the retinal ganglion cells in the damaged eye remained intact.

While either visual stimulation or mTOR-pathway reactivation produced some modest axonal regrowth from retinal ganglion cells in mice's damaged eye, the regrowth extended only to the optic chiasm, where healthy axons exit the optic nerve and make their way to diverse brain structures. But when the two approaches were combined - and if the mouse's undamaged eye was temporarily obstructed in order to encourage active use of the damaged eye - substantial numbers of axons grew beyond the optic chiasm and migrated to their appropriate destinations in the brain. Tests of the mice's vision indicated that visual input from the photoreceptor cells in their damaged eye was reaching retinal ganglion cells in the same eye and, crucially, being conveyed to appropriate downstream brain structures essential to processing that visual input. In other words, the regenerating axons, having grown back to diverse brain structures, had established functional links with these targets. The mice's once-blind eye could now see. However, even mice whose behavior showed restored vision on some tests, including the one described above, failed other tests that probably required finer visual discrimination.

Link: http://med.stanford.edu/news/all-news/2016/07/first-ever-restoration-of-vision-achieved-in-mice.html