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Restaurer cellules et rétines?
Severed optical nerves can be made to grow again
19:00 05 December 01
James Randerson
     It is being hailed as one of the most significant advances in nerve regeneration in a decade. After severing an optic nerve in rats, neurologists have found a way to reconnect it to the brain so that it once again transmits normal electrical signals.
     The achievement is a first in mammals, and may hint at ways of reversing some types of blindness in people. Scientists also hope to use a version of the technique to treat people with spinal cord injuries.
     In many simple creatures, damaged nerves mend themselves. But mammals, with their large brains, have traded this flexibility for stability. With such a complex nervous system, rewiring damaged nerves the wrong way could do more harm than not rewiring at all. So mammals keep a lid on nerve cell growth by producing proteins that inhibit axons--the part of a nerve cell that conducts signals--growing in the scar tissue that forms after injury.
     Now a team led by Solon Thanos at the University of Münster in Germany has got severed nerves to regrow up to 14 millimetres--more than three times as far as anyone has managed before. They first anaesthetised rats and severed their optic nerves. Then they sutured the two cut ends back together to repair the connective tissue sheath surrounding the nerve. Finally they punctured the lenses in the rats' eyes which releases proteins called crystallins.

"Astounding growth"
     The proteins are known to inhibit apoptosis - the mechanism by which cells self-destruct - but Thanos thinks they also promote regrowth in the axon by blocking receptors for growth-inhibiting proteins at the growing tip of the nerve.
     Previous studies by Larry Benowitz at Harvard Medical School have shown that injury to the lens can stimulate optic nerves to grow by up to 4 millimetres. He says the German researchers have achieved "astounding levels of axon growth" with their technique. But he disagrees with their explanation of how it works. Benowitz thinks that the axons are stimulated by the inflammatory immune response triggered by the surgery, rather than by any inhibiting effect of crystallins.
     Whatever the mechanism, three months after the surgery, about 30 per cent of the nerve fibres had regenerated. This included all major cell types, including those carrying colour and contrast information from the eye to the brain. "Even 10 per cent is sufficient for residual sight," says Thanos.
     The regenerated nerves also carried normal electrical signals, suggesting that they had rewired themselves into the brain, although the connections were a bit scrambled. The team is currently studying the rats' behaviour to assess how good their eyesight is.
     Jerry Silver, a nerve regeneration expert at Case Western Reserve University in Ohio, says the crucial question now is whether the findings can be applied to other parts of the nervous system.
More at: Experimental Neurology (vol 172, p 257)
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Converted iris cells could restore damaged retinas
09:46 12 November 01
Emma Young
     Iris cells can be tweaked to imitate retinal cells, raising the prospect of using a patient's own tissue to treat damaged retinas, say Japanese researchers.
     In the developing eye, the inner layer of the "optic cup" differentiates into the retina and the iris. "This common developmental origin prompted us to test whether iris tissue could give rise to retinal tissue," Masayo Takahashi of Kyoto University and his colleagues write in the journal Nature Neuroscience.
     The team extracted iris tissue from adult rats' eyes, a relatively straightforward procedure. Then they used a modified virus to introduce into the cells a master switch gene expressed in mature light-reactive cells in the retina.
     They found that the cells produced rhodopsin, the light-sensitive pigment contained in rod photoreceptor cells in the retina. Ultimately, the team hope that iris cells could be coaxed into producing rhodopsin using chemical factors, rather than gene therapy.

Stem cell failure
     "Our results have opened up the possibility of autograft of photoreceptor cells, however we still have a long way to go," Takahashi told New Scientist.
     Autografts involve removing a section of tissue from a patient and grafting it somewhere else on their body. Retinal transplants from one person to another are currently performed, but there is a severe lack of donors. The potential for immune system rejection of the transplanted tissue is also a problem.
     Iris cells offer the best hope for retinal autografts, says Takahashi. Attempts to create photoreceptors from neural stem cells, for example, have so far failed.
     Age-related macular degeneration, which involves a wearing out of light-sensitive rod and cone cells, is one of the commonest causes of blindness in the west and affects 30 per cent of people over 75. The only cure is to transplant healthy cells into the damaged area.
Journal reference: Nature Neuroscience (DOI: 10.1038/nn762)