Three Blind Mice: See How They . . . See

by Scott P. Edwards

January, 2007

In a scientific first, researchers based in London have restored vision in mice by transplanting light-sensitive photoreceptor cells in their eyes. Although human application is not assured, the finding is a significant first step.

The scientists used stem cells from a stage when the retina is forming to restore vision in the mice, which were affected by photoreceptor loss, the most common cause of blindness in humans. Photoreceptors, commonly known as rods and cones, are specialized nerve cells located at the back of the eye in the retina.

Rod cells are most sensitive to light and dark changes, while cone cells respond more to colors. Photoreceptor loss leads to diseases such as retinitis pigmentosa and age-related macular degeneration.

“Photoreceptors are the first cells of vision,” says Anand Swaroop of the University of Michigan Medical School, who collaborated on the British study. “These cells sense light. If they die, you go blind.”

Timing Determines Cell Fate

Scientists believe the retina is an ideal spot to try stem cell therapy because wiring to the brain remains intact, at least initially, after photoreceptor loss. Therefore, researchers at the University College London (UCL) Institute of Ophthalmology thought transplanted photoreceptors would need to make only one short connection to restore vision in the mice, which lacked photoreceptors because of genetic defects.

Previous attempts to restore vision via stem cell transplants had proved fruitless, however, because the stem cells did not develop enough to integrate into their new environment and grow into functioning photoreceptors. The British researchers, led by Robin Ali of UCL and Robert MacLaren, an eye surgeon at London’s Moorfields Eye Hospital, transplanted cells at a later stage of development when they were more likely to develop into photoreceptors. The cells were taken from healthy mice only after they had begun to produce rhodopsin, a light-absorbing pigment, they reported Nov. 9 in Nature.

“We worked on the theory that cells at a later stage of development might have a higher probability of success upon transplantation,” Ali says. “We showed that cells taken from the peak rod genesis stage of development, when the retina is about to be formed, can be successfully transplanted and integrated into the adult or degenerating retina.”

The stem cells were removed from three- to five-day-old mice at a stage during which they were generating photoreceptors, then were transplanted into adult mouse retinas. Clinical examinations determined that cells produced within a few days of birth generated the most new photoreceptors and that, following transplantation, they connected to the retina appropriately and helped restore vision.

In age-related macular degeneration, photoreceptor cells in the macula die slowly, accounting for the disease’s primary characterization: progressive loss of central vision. Most cases of retinitis pigmentosa (RP) are caused by progressive degeneration of rod cells, leading to the loss of peripheral vision. Other forms of RP lead to the loss of central vision, as well as disturbances in color perception, that cannot be corrected.

Ali and MacLaren say their findings show that the mature retina, previously thought to have no capacity for repair, can in fact support the development of new functional photoreceptors. Thus, the transplantation of photoreceptor cells may be able to restore vision for individuals who have lost their sight to macular degeneration, retinitis pigmentosa, and other eye diseases.

Caution in Humans

These findings do not necessarily mean that photoreceptor transplantation will work as successfully in humans as it did in mice, scientists caution. MacLaren says the research shows that “photoreceptor transplantation is feasible,” but it is not yet clear where the retinal stem cells will come from.

The options include growing embryonic stem cells to the appropriate stage of development for transplantation in the laboratory or using cells found on the margin of the adult retina that have stem cell–like properties. This latter group of cells could be harvested through a minor surgical procedure, grown in the lab to become photoreceptor precursor cells, and then transplanted into the diseased retina.

“We don’t know if embryonic stem cells are better than adult stem cells for these transplants or vice versa,” says Swaroop. “Both have a lot of potential. Embryonic stem cells are more intuitive, but adult stem cells may work, as well.”

Swaroop, for one, is cautiously optimistic: “Perhaps within the next five years we will begin to see the first steps toward retinal cell transplants for people with blinding eye disease.”