Scientists say they've restored the vision of blind mice by introducing light-sensitive cells into the rodents' retinas. These "photoreceptor precursor cells" are not undifferentiated stem cells but come from a later stage of cell development when stem cells have already "committed" to being a particular cell type -- in this case the rod-and-cone photoreceptors the eye uses to sense light.
The study invigorates the search for cell transplants that might someday restore the vision of millions of people who suffer from a loss of these photoreceptors. "We think this is a major breakthrough because it shows what can be achieved," said study lead researcher Dr. Robert MacLaren, a consultant vitreoretinal surgeon at Moorfields Eye Hospital and a clinician scientist at the University of London, in England. The finding also gets around the thorny ethical question of using embryonic stem cells. In fact, MacLaren said, "we do not want embryonic stem cells because they are too undifferentiated."
One expert had high praise for the study. "MacLaren's stunning report will re-rejuvenate photoreceptor transplantation research, and may even transform our clinical practice and restore activities of daily living in individuals with retinal degeneration," said Dr. Steven Tsang, assistant professor of clinical ophthalmology at the Columbia University Medical Center in New York City. The findings were published in the Nov. 9 issue of Nature.
Stem cells continue to intrigue scientists because of their ability to develop into any cell type in the body. The tantalizing promise of stem-cell therapy lies in its potential to replace cells or tissues damaged by disease or injury. The millions of photoreceptors in the eye act as the retina's "pixels," interpreting incoming light and hooking up with nerve cells to transmit that information to the brain. But myriad illnesses -- everything from diabetes to age-related macular degeneration -- can kill off these cells, triggering partial or full vision loss.
Scientists have tried introducing embryonic or adult stem cells into the retina before, in the hope they might develop into photoreceptors and make the connections needed to restore sight. Those experiments failed to work, however. According to MacLaren, the problem may have been in the timing. He explained that prior stem cell efforts used cells that had not yet reached that stage where they were committed to develop into a particular cell type. In contrast, "we are transplanting cells at the exact time that they are destined to become photoreceptors -- i.e., they are past the point of no return," MacLaren explained.
In the experiment, his team harvested these photoreceptor precursor cells from the retinas of newborn mice, whose eyes were still developing. They then transplanted these cells into the "subretinal space" of the eyes of blind mice. These mice had certain gene defects that left them with few working photoreceptors. "These cells were transplanted extremely quickly (i.e., 30 minutes out of their normal environment)," MacLaren said. This rapid transfer, plus their positioning in a conducive retinal environment, means that the cells "were able to form quick connections with host cells," he said. It's those connections that allowed progenitor cells to develop into working photoreceptors and then form tangible, functioning neural connections with the rodents' brains. The result: The pupils of these formerly blind mice began to react to even low levels of light in their environment, the researchers reported. Light stimuli also began to spark new activity in brain cells associated with vision.
MacLaren's group had also attached a green fluorescent genetic "tag" to the transplanted cells. This allowed the scientists to observe the cells' progress as they started making connections to other cells within the eye. While this study used photoreceptor precursor cells extracted from the eyes of newborn mice, MacLaren is confident that adult stem cells could also be genetically manipulated to produce high numbers of precursor cells in the lab. In fact, the next step in this research focuses on getting "more photoreceptor progenitor cells from in vitro gene transfer," he said. "We might need stem cell biologists to get these cells for us, or we might be able to find them within the adult human eye." Tsang is optimistic that the research presented by MacLaren's group "will pave the way for clinical use of stem cell derived photoreceptors. Their exciting results will revive interest in photoreceptor transplantation."
