Scientists are taking the first major step in using stem cells to replace retinal cells lost to degenerative eye diseases such as macular degeneration and retinitis pigmentosa. According to findings published today, researchers at the University of Washington in Seattle can reliably make retinal cells from embryonic stem cells. The researchers are now implanting the cells into blind animals to see if the cells can restore vision.

“This work is the first step toward retinal reconstitution,” says Stephen Rose, chief research officer at the Foundation Fighting Blindness, a nonprofit funding agency based in Owings Mills, MD.

The retina is a layer of cells lining the back of the eye that contains specialized neurons, known as photoreceptors, to convert light into electrical signals, as well as other neurons, known as retinal ganglion cells, to send those messages to the brain. In age-related macular degeneration and retinitis pigmentosa, the photoreceptors degenerate over time, leading to loss of vision.

“Those are the diseases we think can be targeted by stem cells,” says Thomas Reh, a developmental biologist at the University of Washington who led the work. “If we can replace the photoreceptors, we think we can restore vision.”

Scientists have been attempting to transplant eye cells for decades. While they have had some success in animal models using cells derived from fetuses or other sources, there has been little progress in humans, largely because of a lack of cells. “Finding a fountain source of cells you can effectively get out of bottle and squirt into someone’s eye is really the way to go,” says Raymond Lund, a retinal cell expert at the Oregon Health and Science University in Portland, OR.

Generating large numbers of retinal cells from embryonic stem cells could solve that problem. Achieving this feat with human cells has been difficult – generating each type of tissue from stem cells requires its own special recipe, and some cell types are more difficult to make than others. Reh and his team used cues from normal eye development to find a unique mix of ingredients that trigger retinal cell development. The key, says Reh, is three proteins, called growth factors, known to be involved in head and eye development.

According to a paper published today in the Proceedings of the National Academy of Sciences, the researchers can reliably generate retinal progenitor cells, which then have the ability to turn into any cell type in the retina, such as photoreceptors, retinal ganglion cells, or other cells. Preliminary results show that when the cells are transplanted into retinas either in a dish or in live animals, the cells migrate to different layers of the retina and begin to express proteins characteristic of the resident cells, including photoreceptors. The researchers are also developing ways to efficiently turn the progenitor cells into photoreceptors in a dish.

The researchers don’t yet know if the cells can actually integrate into the complex circuitry of the eye to restore vision, but early results are promising. The transplanted cells do express many of the proteins needed to respond to light, and they make neural connections when grown in a dish with other retinal cells. However, the true test will come with Reh’s current experiments: transplanting the cells into blind animals. “We should know within the next year if the cells can restore vision,” says Reh.

Other groups are also developing stem cell therapies for the retina. Advanced Cell Technology (ACT), a stem cell biotechnology company based in Alameda, CA, has developed a way to turn embryonic stem cells into pigment epithelial cells, another cell type lost in macular degeneration.

When implanted into the eyes of animal models, the cells protect against further degeneration of the photoreceptors and improve vision, says Robert Lanza, vice president of research and scientific development at ACT. The company plans to file for permission from the Food and Drug Administration to start human trials of the therapy by the end of next year, he says.

Experts say that work such as Reh’s and Lanza’s is finally bringing hope to an area of research that has struggled for years. Scientists have had some success in transplanting retinal cells from fetuses in animal models, and a small clinical trial of this type of therapy is currently underway. “But the logistics of using fetal tissue has a lot of uncertainties and ethical issues, and there is always the danger of transmitting infective agents to the host,” says Lund.

Stem cell-derived retinal cells provide a much larger and more reliable source of cells. “I think cell therapies for eye disease are really going to take off in the next few years,” says Lund.

Reh and others still have a lot to work out before stem cell therapies for retinal degeneration become a reality. For example, it’s not yet clear whether it’s better to implant cells when they are still in a somewhat undifferentiated state, such as the progenitor cells, or whether it is better to turn the cells into photoreceptors and then transplant. Reh plans to try both.

Restoring vision could be one of the most promising early uses of stem cell therapies because scientists know exactly what cells they need to replace. “We’re always reading that embryonic cells are going to cure every disease,” says Lund. “But in this case, we’re clearly working with the idea that embryonic stem cells will have very specific functions in eye disease.”