Regenerative medicine research offers hope for the blind

Published on April 19, 2012 at 4:55 PM · No Comments

By Dr Ananya Mandal, MD

Researchers in Britain have successfully renewed a level of sight in visually impaired mice, opening the possibility that the same can be achieved in humans.

The University College London researchers transplanted immature vision cells directly into the mouse retina. They noted that within weeks the cells began to integrate into the retina and the researchers, led by Prof Robin Ali in the university’s Institute of Ophthalmology, were able to show that vision began to return to the mice.

The cells in question are known as photoreceptors and are lost in very common degenerative diseases such as retinitis pigmentosa, age-related macular degeneration and diabetic retinopathy, said Anna Moran, external affairs manager at Irish medical charity Fighting Blindness. At least 100,000 people here are affected by these conditions. Prof Ali receives funding from Fighting Blindness and is also the body’s associate director of research. This work was funded directly by the UK Medical Research Council and details are published today in the journal Nature.

The team explains that the eye has two types of photoreceptors: rod cells and cone cells. The UCL team collected immature rod photoreceptor cells from healthy donor mice and transplanted them into the retinas of the vision-impaired mice. The undeveloped precursor cells used in the study were taken from week-old mice. Up to 32,000 of the cells were integrated into the retinas of recipient animals.

After four to six weeks the transplanted cells had formed connections to the optic nerve and were working almost as well as rod cells in healthy mice, the researchers found.

To see how the transplants affected behavior, mice were placed in a dimly lit Y-shaped water maze in which one of two routes led to escape. This required swimming towards a visual cue, a grating pattern. Mice with transplanted cells were able to find a raised platform much more quickly than mice without the transplanted cells. Untreated mice swam in circles, proving the treated ones could see the way out.

“We have shown for the first time that transplanted photoreceptor cells can integrate successfully with the existing retinal circuitry and truly improve vision,” Prof Ali said. Researchers were taken aback by the results. “It is restoring visual function and to a much higher degree than they expected,” Ms Moran said. “Fighting Blindness has been supporting vision research for 30 years and this is probably the most important finding in that time,” Ms Moran said.

David Head, chief executive at the retinitis pigmentosa charity RP Fighting Blindness, which part-funded the research, said, “This is fantastic progress and exciting for patients faced with sight loss as a result of retinitis pigmentosa. To read that cells appeared to be functioning almost as well as normal rod-photoreceptor cells and had formed the connections needed to transmit visual information to the brain is truly amazing. This is a great step forward.”

The work is at an early stage but if successful hundreds of thousands of Britons could benefit, such as those with age-related macular degeneration – one of the most common forms of blindness. Prof Ali hopes to use embryonic stem cells to produce transplant tissues to renew damaged retinas. The British and American scientists say much more work is needed before the technique can be attempted on human patients. The first clinical trials might be five or 10 years away.

Professor Phil Luthert, director of the UCL Institute of Ophthalmology, said, “This is a landmark paper and the techniques used here are part of a pretty big push in regenerative medicine. It was only a few years ago that we wouldn't have thought repairing adult systems in this way would be possible - it was assumed to be a bridge too far, but with retinas at least, it seems entirely feasible.”

“What is truly remarkable about this field is how well transplanted cells seem to be accepted by the retina where they move into the right place and effectively wire themselves up. The next challenges faced by scientists in this area concern how many cells can be got into the retina, how well they can be made to connect and then to see just how effectively they will work. We also do not know how long-term any effects will be, whilst we have good reason to believe that any procedures would be long-lasting, at this stage we are only speculating.”

Researchers wrote in the journal Nature, “The results presented here demonstrate for the first time that transplanted rod-photoreceptor precursors can integrate into a dysfunctional adult retina, and, by directly connecting with the host retinal circuitry, truly improve vision.”

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