Vision restored in mice using later stem cells

In groundbreaking research, scientists have used a new approach to stem cell science to partially restore vision in mice genetically engineered to mimic human degenerative sight defects such as retinitis pigmentosa and macular degeneration. The team, a collaboration between University College London and the University of Michigan, Ann Arbor, US, transplanted immature retinal stem cells from newborn mice into the eyes of the blinded animals. The transplanted cells successfully implanted and made electrical connections to the brain. Tests confirmed that the animals' pupils responded to light and that signals were present in the optic nerve, showing that information was being successfully transmitted to the brain. It was previously thought that adult retinas had no capacity for repair.

Prior to this breakthrough, researchers unsuccessfully sought to effect changes in a similar way by using very early stem cells. In contrast to this, lead researcher Robin Ali used much later cells - retinal precursor cells - that had stopped dividing. The team identified the best cells to use by transplanting cells extracted from mice at various stages, such as embryos and post-birth. Cells produced in the first few days after birth produced the most new photoreceptors in the recipient mice. Cells from an equivalent human stage would be difficult to obtain as they would need to be extracted from fetuses in the first or second trimester of pregnancy. It has been shown in separate work, however, that it is possible to obtain this stage of differentiated photoreceptors from embryonic stem (ES) cells.

Commenting on the new work, Thomas Reh of the University of Washington in Seattle, said that 'we can derive retina cells, including cells at exactly the stage that Ali's group found were best for transplantation, from human embryonic stem cells', adding that 'joining the approaches would seem to be an important next step in treating retinal degeneration and restoring vision'.

Millions of people suffer from degenerative eye diseases, ranging from age-related macular degeneration to diabetes. At the moment, once the rod and cone photoreceptors have been lost they cannot be replaced. Current treatments involve attempting to delay or slow the loss of these cells. One advantage of transplantation in the retina is that the nerve connections to the brain remain in place for some time even after the loss of the receptor cells. If the correct cells can be identified for transplantation they can 'tap into' this pre-existing structure. Dr Robert MacLaren, one author of the paper, based at Moorfields Eye Hospital in London, said that the research would now focus on adult stem cells to see if they could be genetically altered to act in a similar way to the mouse retinal cells. There are some cells on the margins of the adult retina that the team think could be suitable. Talking about the clinical relevance of the work Dr MacLaren said 'every day I sit in my clinic and have to tell patients that there's nothing I can do', adding 'I don't want to give patients false hope but at least now, if I see a young patient, I can say that there might be something within your lifetime'.