Treating eye injuries with stem cells

Getting in your car to drive to work is not often associated with losing vision. But this is what happens to tens of thousands of Americans who experience head trauma each year, most frequently from motor vehicle crashes. Bike accidents, falls, sports injuries and strokes could also harm the nerve bundle that connects the eye to the brain.

“There’s no therapy that could help regenerate these neurons once they’re lost,” says Y. Joyce Liao, assistant professor of ophthalmology at Stanford University. “The only choice is to think about how to replace them.” Her goal is to provide therapeutic options to people with optic neuropathy, which causes severe vision loss.

One promising avenue of research involves the use of embryonic stem cells, which can become many different cell types. Liao is developing strategies to transplant these cells into eyes with damaged nerve fibers. To help with the process, she uses laser stimulation, a routine treatment for diabetic patients who are visually impaired or at risk for losing their sight. “My idea was that laser therapy could also be used to promote stem cell transplantation in humans in the future,” she says.

 Restoring Sight with Light

The primary cause of sudden loss of eyesight in people over 50 is anterior ischemic optic neuropathy, which is triggered by an interruption of blood flow. Liao developed an animal model of the disease using mice whose optic nerves have been damaged by stroke. To visualize tissue damage, she uses an imaging technique called ocular coherence tomography. Her results indicate that the therapeutic window for optic nerve strokes is short because neurons degenerate more and more every day. “If we want to protect neurons, we have to somehow arrest their degeneration and the disease process and treat the injury very early,” she says. But the timing may not be as critical for stem cell procedures, because the neurons can be replaced after they die.

Once she assessed the damage that optic nerve stroke causes in animals, she went on to test whether combined stem-cell and laser therapy would help. After coaxing embryonic stem cells to start taking on the fate of neurons in a dish, she transferred them into the eyes of the mice. Then she stimulated the eyes with laser pulses of moderate strength. Within two months, the relocated cells matured, repopulated the eye and expressed markers of neurons and support cells called glia. The laser stimulation helps transferred cells adjust to their new environment, Liao says. She’s currently figuring out the best timing for transplantation, and whether the method works for chronic injuries. The big question, she says, is whether the relocated cells make functional connections with nearby cells.

Making a Difference

Because laser procedures have already been approved for diabetic patients, Liao is optimistic about the potential of using the approach in future clinical trials. First, she needs to do research using clinically relevant cells, such as human embryonic stem cells (hESCs). But with the recent legal injunction against using federal money for hESC research, Liao is concerned about the roadblocks that lie ahead (see Q&A in this issue). “I’m disappointed because vision loss is one area where stem cell therapy could really make an impact,” she says.

Unlike many other parts of the nervous system, the eye has functions that are easy to quantify with great precision. By presenting spots of light or letters of different sizes or levels of contrast, scientists can accurately measure improvements in eyesight. “Rescuing a certain part of the visual system may be one of the best ways to determine the success of regenerative medicine,” Liao says.

With federal funding for hESC research in jeopardy, Liao will turn to other sources in the future. “We’ll certainly depend more and more on private philanthropists to push the wave of discovery forward,” she says. “If they’re interested in furthering this cause, they can take a major stand by collaborating with other agencies to make it possible for people like me to translate discoveries in animal models to human treatments.”

Challenges and Rewards

As an assistant professor, Liao appreciates the jumpstart she got from the Burroughs Wellcome Fund, which honored her with the Career Award in Biomedical Sciences in 2005. “If you don’t have money to do research, you could have a lot of good ideas, but you wouldn’t be able to carry them out,” she says. The biggest challenge she faced in setting up her lab two years ago was assembling the equipment and hiring the right team. “Without this funding, my projects would never have even happened.”

After stints at Harvard for her undergraduate studies and the University of California, San Francisco, for her MD and PhD, Liao completed neurology training at Stanford. But she realized that the research she was doing didn’t have a significant tie to patients. She then specialized in neuro-ophthalmology because she wanted to focus her research on challenging clinical problems that lack successful treatments. “I’m driven to make basic discoveries that will have an impact on my patients.”

In the future, she’d like to devote more energy to the Stanford Center for Vision and Blindness Prevention, an inter-disciplinary research group whose mission is to translate advances in basic science into clinical treatments for patients. “Being able to offer them effective therapies and measure how their vision improves is very rewarding.” Liao says. “In the end, I have to answer to my patients.”

By Janelle Weaver