Hamsters blinded following damage to their optic nerve have had their vision partially restored with the help of an implanted nanoscale scaffold that has encouraged nerve tissue to regrow.
The technique, likened by its inventors to the way a garden trellis encourages the growth of ivy, holds out the hope that people with diseased or injured optic nerves might one day recover their sight.
The optic nerve, which connects the eye to the brain, can be severed by traumatic injuries such as those suffered by people in car crashes. It can also be damaged by glaucoma, when excessive pressure in the eyeball causes tissue at the back of the eye to collapse, pulling nerve fibres apart and so causing progressive loss of vision.
Repairing the optic nerve requires the long, spidery branches of nerve cells, called axons, to grow again and reconnect. Achieving this is a "formidable barrier", says Rutledge Ellis-Behnke, a biomedical engineer at the Massachusetts Institute of Technology (MIT), US. Axons can be encouraged to extend by exposing them to growth factors, but they rarely extend far enough to bridge the large gaps typical of most optic nerve injuries, he says.
Growth and migration
To overcome this problem, Ellis-Behnke and colleagues from Hong Kong University and the Institute for Neuroscience in Xi'an, both in China, created a nerve-bridging scaffold, made up of nanoparticle fibres. They attempted to make these fibres the same size as the sugars and proteins on the surface of the torn axon, in the hope that this would encourage cell growth and migration.
To make their scaffold, the team turned to a discovery from the early 1990s by Shuguang Zhang of MIT's Center for Biomedical Engineering. He found that certain sequences of peptides can be made to self-assemble into mesh-like sheets of nanofibres by immersing them in salt solutions at similar concentrations to those found in the body.
To test whether this would help nerves to regenerate, the team took hamsters whose optic nerves had been deliberately severed and injected a peptide mixture into the animals' brain close to the injury site. They found that after six weeks, the animals had recovered some of their vision. "They could see well enough to find their food, to function well," says Gerald Schneider, a member of the team at MIT.
Schneider estimates that 30,000 axons had reconnected, compared with only around 30 in previous experiments using other approaches, such as nerve growth factors. The team speculates that the similarity between the size of the fibres and the features on neural material is what encourages the axons to bridge the gap. The scaffold appears to eventually break down harmlessly.
Tissue engineer Kevin Shakesheff at the University of Nottingham, UK, says the work is "very exciting", but urges great caution. The surgical cut made in the hamster's nerve is not representative of "more messy" injury or disease in people, he warns, and other central nervous system work has shown that species differences mean nerve regeneration in a rodent might not translate into humans.
Shakesheff also notes that how the scaffold regenerates tissue is currently a mystery and that delivering stem cells to further boost the regenerative response might ultimately be an option.
The biggest prize would be if the technique could repair spinal cord injuries, or brain tissue damaged by stroke or other neurological condition. With that in view, the MIT team now plans to extend the work in the hope of developing therapies for some forms of paralysis.
Journal reference: Proceedings of the National Academy of Sciences (DOI: 10.1073/pnas.0600559103)
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