Rats genetically engineered to lose their sight can be protected from blindness by injections of human neural stem cells, according to research presented at the International Society for Stem Cell Research conference in San Francisco last week. StemCells, a startup in Palo Alto, CA, plans to use the positive results to file for approval from the U.S. Food and Drug Administration to begin human trials. The company is already testing the cells in children with a rare, fatal brain disorder called Batten’s disease.
The company’s cells are isolated from human fetal tissue and then grown in culture. To determine whether these cells can protect against retinal degeneration, scientists studied rats that were genetically engineered to progressively lose their photoreceptors–cells in the retina that convert light into neural signals. These animals are commonly used to model macular degeneration and retinitis pigmentosa, two major causes of blindness that result from cell loss in the retina. Researchers injected about 100,000 cells into the animals’ eyes when the rats were 21 days old. According to Alexandra Capela, a scientist at StemCells who presented the work, the cells migrate over time, forming a layer between the photoreceptors and a layer of tissue called the retinal pigment epithelium, cells which nourish and support the photoreceptors.
Using electrodes implanted into the visual system, scientists measured the lowest levels of light the rats could detect. They found that the cells protected vision in the part of the retina in which they were implanted. They also tested the animals’ acuity by examining the maximal speed at which they followed a series of moving bars, a natural rat reflex. “The treated animals maintain a high level of visual acuity, while the untreated animals decline steadily,” said Capela.
The implanted cells don’t actually develop into new photoreceptors; in fact, they appear to maintain their undifferentiated state. So it’s not clear how they protect against blindness. “The neuroprotective effect in the rats is interesting, but the mechanism is still pretty obscure,” says Thomas Reh, a neuroscientist at the University of Washington, in Seattle, who was not involved in the study.
Raymond Lund, a scientist at the Casey Eye Institute at Oregon Health Sciences University who collaborated on the study, says the cells “seem to somehow bypass the defect without actually correcting it.” This may be because the cells make growth factors known to keep damaged cells alive, says Lund, who has also tested the cells in a different animal model of blindness. Another hypothesis is that the cells help clear cellular debris that builds up in the retinas of these rats and harms the photoreceptors.
While the cells seem to survive for months in mice, it’s not yet clear how long they will survive in humans, who live much longer lives, or whether they will affect the long-term function of the retina in other ways. For example, they might interfere with the interaction between the photoreceptors and the retinal pigment epithelium, says Reh.
Because the stem-cell treatment doesn’t replace lost cells, it most likely needs to be administered early in the course of a disease. “This would not be something for advanced macular degeneration, where the receptors are already damaged,” says Lund. “We would want to spot patients who are seriously as risk and hopefully slow or stop process of disease.” A number of genetic factors have been identified that boost risk for the disease, and genetic testing is available.
Taken together, retinitis pigmentosa and macular degeneration are the most common causes of blindness in people 40 and older. No treatments yet exist for the most common form of macular degeneration, which accounts for about 90 percent of cases. A number of novel therapies are under development, including drugs, cell transplants, and implanted devices. Advanced Cell Technology, based in Worcester, MA, uses human embryonic stem cells to grow retinal pigment epithelium, often the first cell type to die off in age-related macular degeneration and other eye diseases. The company filed for permission to begin clinical trials of the cells last November.