Larry Benowitz, a professor of surgery and ophthalmology at Harvard Medical School, has been working on nerve generation in mice for years. His latest experiment involves mice blinded in one eye after their optic nerves were artificially damaged.
A paper that appeared in the Proceedings of the National Academy of Sciences on Monday describes how Benowitz and his colleagues coaxed the mouse's retinal ganglion cells - located near the inner surface of the retina - to regenerate and grow into the brain, restoring some visual function.
In a phone interview, Benowitz was quick to emphasize that the breakthrough isn't nearly ready to be tested on human subjects. He usually gets flooded by calls from hopeful patients after one of his papers hits the presses or the web, but has to turn them away.
What did here isn't ready for prime time, clinically speaking, Benowitz warned.
The technique for making the retinal ganglion cells grow again requires three elements. The first of these is inflammation, which the scientists induce by injecting a substance called Zymosan in an area just behind the edge of the iris of the mouse's eye.
It's not something you'd want to try at home, Benowitz says.
The inflammatory response provokes the cells to release a potent growth factor called oncomodulin, which stimulates cell growth. (Benowitz hopes that someday researchers might be able to transform cells to release this growth factor without inducing inflammation.)
Researchers also injected the mice with CPT-cAMP, a molecule that enhances the growth-stimulating abilities of oncomodulin. CPT-cAMP is thought to play a key role in the molecular signaling chain that moves receptors for oncomodulin from inside the cell to the cell membrane, where they can be bound by the growth factor.
The last piece of the puzzle was deleting a gene called PTEN, which normally puts the brakes on cell signaling. Normally, this is a good thing - PTEN's primary job is to suppress the kind of uncontrolled growth that leads to tumors. But in this instance, the scientists needed to take the brake off in order to activate the growth pathway.
Benowitz said the key test here wasn't whether nerve fibers could regenerate - it was whether or not the nerves would be able to find their way once they started growing. During embryonic development, nerves are directed to the right places thanks to an array of complex chemical signals.
No one knew if the navigation system that nerve fibers use to find the right places to hook up remains once the brain is fully developed, he said.
But the regrown nerves managed to make contact with several visual centers of the mouse brains, and the mice regained a degree of visual function, including depth perception.
This kind of technique would have limited applications for humans, since it only works where damage is limited to the optic nerve. Plus regrowth is possible only within a limited time window - persons blind from birth would be out of luck.
Still, Benowitz says, It's a proof of principle that rewiring the visual system may be possible.