BioWorld International Correspondent
LONDON - Mice that were blind had some sight restored after receiving transplants of cells into their eyes. The cells were destined to become the light-detecting retinal cells known as photoreceptors, but had not fully developed into mature photoreceptors when the transplants took place.
The work, hailed as a major breakthrough, hastens the day when people who are blind because they have lost photoreceptor cells from their retinas - as a result of conditions such as age-related macular degeneration and many genetic eye diseases, for example - could be treated with cell transplants.
One strategy for humans could be to use embryonic retinal cells at the appropriate stage of development, but the researchers said it might be possible to avoid that approach. Robin Ali, of the University College London Institute of Ophthalmology and a member of the team that carried out the research, said: "Recent research has shown that a population of cells can be found on the margin of the adult retina which have stem cell-like properties; in other words, they are capable of self-renewal. These could be harvested through minor surgery and grown in the lab to become photoreceptor precursors before being re-implanted on the retina."
The cells transplanted into the eyes of the mice not only survived but made appropriate connections to nerves leading to the brain. Mice treated with the transplants regained the reflex whereby the pupil of the eye constricts when a light is shone on the retina.
An account of the team's experiments appears in the Nov. 8, 2006, Nature, in a paper titled "Retinal repair by transplantation of photoreceptor precursors."
Robert MacLaren, an author of the paper and a consultant eye surgeon at Moorfields Eye Hospital and the University College London Institute of Ophthalmology in London, said: "This research is the first to show that photoreceptor transplantation is feasible and has the potential to restore vision. We are now confident that this is the avenue to pursue, to uncover ways of restoring vision to those who have lost their sight, although a clinical treatment is still a long way off."
MacLaren said numerous experiments in which stem cells had been injected into the space under the retina had been unsuccessful. No one knew whether that was because the stem cells had failed to differentiate into photoreceptor cells, or whether they had differentiated but failed to make any connection with cells in the optic nerve.
The team therefore decided on a slightly different approach and set out to discover if using cells that had been programmed to become photoreceptor cells, but which had not fully differentiated, would make any difference.
As recipients for the transplants, the scientists used mice that were blind due to a genetic defect that left them with a disease similar to the human disease called retinitis pigmentosa. The cells used for the transplant were from the retinas of newborn mice, taken at a time when the rod photoreceptor cells are known to be developing, but not yet formed.
Anand Swaroop, from the University of Michigan, provided the strain of mice used for the donor cells. They had been modified genetically so that cells that developed into mature rod photoreceptors would fluoresce green.
The researchers injected the donor cells into the subretinal space of the recipient animals. Subsequent tests showed that the transplanted cells had not only survived, but also made appropriate connections to host cells.
MacLaren said: "Reconnecting nerve cells to the complex electrical circuitry of the human brain has always been a major challenge in neural transplantation. It now appears that this can be done, at least in the retina."
Photoreceptor cells are the easiest neurons to transplant, MacLaren explained, because they are stimulated by light and then connect with other cells in only one direction. Their axons are short, and if they are placed in the right location, it is a simple matter for them to make connections with the first neurons they encounter, which are the correct ones.
Further tests showed that the recipient mice had regained a reflex that indicated that they could see: Shining a light in their eyes resulted in constriction of their pupils.
One limitation of the experiments reported in Nature is that they used only cells destined to be rod photoreceptors, which mainly detect light and dark. If the technique is to be useful for the treatment of blindness in humans, however, it will be important to be able to transplant cone photoreceptor cells, as, in humans, those are important in color vision and the ability to see in fine detail.