Timing may be everything when it comes to restoring lost eyesight through stem cell therapy.

In a new study, retina stem cells harvested at a particular stage of development successfully restored visual function in mice affected by a common cause of blindness also found in humans, known as photoreceptor loss.

Although earlier attempts at retina transplantation using embryonic stem cells failed, the researchers say that by using stem cells at a later stage of development, they were able to repair damaged retinas in the mice.

“We worked on the theory that cells at a later stage of development might have a higher probability of success upon transplantation” says researcher Robin Ali of the University College London Institute of Ophthalmology in a news release.

“And we show here that cells taken from the peak rod genesis stage of development, when the retina is about to be formed, can be successfully transplanted and integrate into the adult or degenerating retina,” says Ali.

Researchers say the findings challenge the assumption that early embryonic stem cells are the best option for tissue repair and may have implications for other types of stem cell therapy and transplantation.

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Retina Transplants

Photoreceptor loss is a form of retina damage implicated in many causes of blindness in humans, from age-related macular degeneration to diabetes.

This type of blindness has been considered irreversible because the mature retina was believed to have no ability to repair itself or to support development of new photoreceptors, which are light-sensing cells.

Previous attempts to generate new photoreceptors using brain and retina stem cells – cells with the ability to become a number of different types of cells -- have failed because the stem cells didn’t integrate into their new environment or develop into photoreceptor cells.

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In this study, researchers took stem cells at later developmental stages and transplanted them into adult mice with photoreceptor loss.

Their results suggest there is a particular time window of development for transplant success in restoring sight to the blind mice.

In the study, cells harvested during this window were able to form new connections within the mature retina and improve the blind mice’s visual responses to light.

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In a commentary accompanying the study in the journal Nature, Thomas A. Reh, of the University of Washington School of Medicine, says the results provide hope for cell-based treatments of retinal disease.

The study also has implications for transplantation strategies in other areas of the central nervous system, he says.

The specific time a cell is harvested may make all the difference in stem cell therapy and transplantation success, Reh says.

Rather than injecting undifferentiated stem cells into damaged tissue, using precursor cells from a later stage of development -- ones already “programmed” to become retina or some other type of cell -- may be more successful, he says.

“These results provide the best evidence so far that cell-replacement therapy may be possible,” writes Reh.

“But there’s a catch,” he adds. “If this scenario were to be applied to humans, one would have to obtain newly generated [photoreceptor] rods from the state of development comparable to postnatal days 3-7 in the mouse [as in the study].

“This is likely to be in the second trimester [in humans] and is clearly not feasible,” writes Reh. Harvesting such cells would mean taking them from a fetus or aborted fetus three to six months into a pregnancy.

However, recent research suggests it might be possible to generate such cells from human embryonic stem cell lines under the right conditions.

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By Jennifer Warner, reviewed by Louise Chang, MD

SOURCE: MacLaren, R. Nature, Nov. 9, 2006, online advance edition. News release, Medical Research Council. News release, University of Michigan Health System.