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Updated 10:00 AM November 13, 2006
 

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  Research

See how they see: Transplanted cells restore visual function in mice

Scientists successfully have transplanted light-sensing cells called photoreceptors directly into the eyes of mice and restored their visual function.

The achievement is based on innovative technology in which the cells are introduced at a particular stage in their development. It was carried out at the London Institute of Ophthalmology using an approach developed at the Kellogg Eye Center to tag rod precursor cells and prepare them for transplantation.

The team of scientists found that transplanted photoreceptor precursor cells survived and became integrated into the mouse retina—and that the technique succeeded because the cells were isolated when they had reached a certain level of maturity.

Rather than injecting undifferentiated and uncommitted stem cells into the retina in hopes they would develop into photoreceptors, researchers introduced cells at a somewhat later stage. These cells are referred to as "precursors." They are immature cells that are programmed to be, but have not yet become, functionally mature photoreceptors—the light-sensitive cells in the retina that are essential for sight.

The findings, reported in the Nov. 9 advance online issue of Nature, come from the collaborative research of Anand Swaroop, the Harold F. Falls Collegiate Professor of Ophthalmology and Visual Sciences at the Medical School, and Robin Ali, professor, Division of Molecular Therapy at the Institute of Ophthalmology in London.

The technology represents a breakthrough in transplantation-based therapies for neurodegenerative diseases. It suggests that scientists may need to introduce changes in stem cells in order for them to become highly specialized neurons.

Although the experiment has implications for human eye diseases that dim the sight of millions of people, Swaroop anticipates several years of research using animal models and cell culture systems still will be needed before transplantation can be considered ready for testing in humans.

Restoring visual function in animals is an important advance, but the scientists caution that it shouldn't be considered the same as restoring vision in humans. The next wave of research will focus on characterizing the mechanisms that generate photoreceptor precursors from stem cells. Swaroop believes the research has potential for developing therapies for people with retinal and macular degenerative diseases that are untreatable today.

The Swaroop research team started to develop its approach to transplantation about six years ago. "Rather than focusing on stem cells," says Swaroop, "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. This technique gives us new insights in repairing damage to the retina and possibly other parts of the central nervous system."

Ali, Swaroop and their colleagues report that transplanted cells in diseased mouse retinas have met several essential requirements: the cells survive; correctly develop into rod photoreceptors; integrate and connect in sufficient numbers to neurons that ultimately carry visual signals to the brain; and they have proven to be functional.

In 2001, Swaroop's team first showed that the gene NRL, discovered several years earlier in his lab, is essential for the development of rods. In its absence, all rods were converted to cones.

Earlier this year, Drs. Masayuki Akimoto and Hong Cheng in the Swaroop lab published a study describing the birth of rod cells. Building on previous research, they were able to make this process visible by using an NRL gene regulatory element to tag the rods with a green fluorescent protein. This enabled Kellogg scientists to illuminate the rods, which begin as unspecified cells and gradually differentiate into cells dedicated to light reception.

The collaboration with Ali's group, funded by the UK's Medical Research Council in London, was critical in testing the next phase of the research. The goal was to learn whether transplanting cells isolated at a specific time period would increase the chances that precursor cells would develop into functioning rods and integrate in the retinal milieu.

The new paper shows that only one group of cells remained viable: those that were not yet mature, but had developed to the point at which they were committed to becoming rods.

Swaroop's research is supported by grants from the National Institutes of Health, Foundation Fighting Blindness, Sramek Foundation and Research to Prevent Blindness.

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