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Stem-cell transfer breakthrough raises hopes for blindness cure

Science Editor,Steve Connor
Thursday 09 November 2006 01:00 GMT
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A breakthrough in restoring sight to the blind has been made with a study showing that a damaged eye can be repaired by transplanting light-sensitive cells. The results of an experiment on laboratory mice have been so successful, scientists believe clinical trials on blind people could start within 10 years.

If the breakthrough can be developed further it could lead to new forms of treatment for the 300,000 visually impaired people in Britain who suffer from age-related macular degeneration and the thousands of blind children with inherited diseases such as retinitis pigmentosa.

Mice that were born blind because of a genetic condition were able to see light for the first time after a revolutionary transplant operation involving stem cells ­ the key cells that develop into the light-sensitive tissue of the eye's retina.

The scientists behind the research believe that it is the first time that nerve cells at the back of eye have been successfully transplanted to restore vision, a development that promises to help millions of blind people throughout the world. "The most important thing is the principle that it can be done," said Robert MacLaren, a consultant surgeon at Moorfields Eye Hospital in London, who was part of the Anglo-American research team.

"We've discovered a biological principle, a healing mechanism that we can take advantage of, but it's still a long way to go before we can apply this to people. We are now confident that this is the avenue to pursue to uncover ways of restoring vision to thousands who have lost their sight."

The study, published in the journal Nature, involved blind mice that were born without light-sensitive "photoreceptors", which detect light when it reaches the retina and send the appropriate signals to the brain via the optic nerve.

Stem cells from the eyes of normal mouse foetuses were cultured in the laboratory before being transplanted to the eyes of the blind mice. Tests showed the stem cells developed into mature photoreceptors of the retina and could transmit signals to the brain.

Previous attempts at transplanting stem cells to a damaged retina had failed, it is believed, because the cells were too immature. The key difference with the latest research is that stem cells were transplanted after they had already developed along the route to becoming photoreceptors, Mr MacLaren said.

"We got them at the point of no return. It is the first time anyone has shown that it is possible to transfer photoreceptors successfully and timing was crucial," he said.

The 100 million photoreceptors of the human retina are like the pixels of a 100-megapixel digital camera and they come in two forms ­ cone cells for seeing colour in daylight and rod cells for seeing black and white in low light.

The study on the mouse only transferred rods ­ which are more common in mice, a nocturnal animal ­ so the scientists have yet to demonstrate that the technique will work with cones, the most important cells for discerning images at the centre of the human retina. It is hoped that to help people with age-related macular degeneration it may only be necessary to transplant the relatively small number of cones in the central part of the retina that are important for good daylight vision.

In the mouse experiment, the scientists knew that the mice could see some light because their pupils contracted and dilated in response to differences in light intensity, showing that the brain was actively processing information from the eyes.

"Remarkably we found that the mature retina, previously believed to have no capacity for repair, is in fact able to support the development of new functional photoreceptors," said Jane Sowden of the Institute of Ophthalmology at University College London (UCL).

Professor Robin Ali of UCL said that in future human clinical trials it may be possible to use embryonic stem cells, or even adult stem cells from within a patient's own eye, for the first transplant operations.

Mr MacLaren said that one obvious advantage of using a patient's own stem cells for the operation was that it would avoid the complication of tissue rejection.

Professor Anand Awaroop of the University of Michigan at Ann Arbor, who collaborated on the study, said the findings may lead to new ways of treating other diseases of the central nervous system.

"Rather than focusing on stem cells, we believed that if we could understand how cells develop and become photoreceptors or any other specific neuron our transplantation efforts would meet with greater success," Professor Awaroop said. "This technique gives us new insights in repairing damage to the retina and possibly other parts of the central nervous system," he said.

How sight is lost

* Macular degeneration affects about 500,000 people in the UK.

* The macula is at the centre of the retina, where the light is focused, and is essential for reading and writing and seeing colour.

* In affected individuals, delicate cells at the centre of the macula stop working for unknown reasons.

* Most cases are of the slow-progressing dry kind; there is no treatment.

* Wet macular degeneration is faster and affects 27,000 new patients a year.

* Most of these patients can now be helped by laser treatment, photodynamic therapy or drugs.

* Most patients pay for drugs because the National Institute for Clinical Excellence is not due to issue guidance on their NHS use until autumn next year.

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