Stem cells give sight to blind mice, raising hope for aging humans

High above the downtown clamour, in one of Toronto’s shiny glass towers, modern medicine’s pioneers have put a whole new spin on an old nursery rhyme.

Using stem cells salvaged from the retinas of human cadavers, researchers with the University of Toronto have restored sight to the eyes of, well, three blind mice. The feat, aside from indicating a quirky sense of humour, has been repeated several times over the last year and marks an important step toward the goal of restoring sight in people.

How stem cells can restore sight


“All the basic biology of the human eye and retina is the same as it is in the mouse,” says study leader Derek van der Kooy, professor of molecular genetics at U of T and senior scientist at the McEwen Centre for Regenerative Medicine. “If we can get enough of the cells to grow and integrate, I think we’d go right into [trials with] humans.”

The Toronto group is hardly alone in its ambitions. Helping the blind to see has become one of the hottest areas of stem cell research. Across Canada, scientists have teamed up to regenerate human eye tissue with adult stem cells and those reprogrammed to behave like embryonic stem cells. Drug giant Pfizer Inc., in one of big pharma’s first forays into stem cells, is backing Britain’s Project to Cure Blindness. And this month, in a rare move, the U.S. Food and Drug Administration gave a Massachusetts company permission for an embryonic stem cell trial to treat Stargardt macular dystrophy, a form of hereditary blindness.

“The progress of the last three years has been incredible,” says Sharon Colle, CEO of the Foundation Fighting Blindness, which helps fund Canada’s stem cell researchers, including Prof. van der Kooy’s team.

In part, researchers have set their sights on the eye as an early target for stem cell treatment because it is somewhat protected by the blood-brain barrier, and tissue transplanted there is less likely to face immune rejection. But a greying population has also made the work a priority. Age-related macular degeneration is the leading cause of blindness in people over 60, and the market for any stem cell treatment to slow or reverse it could be massive.

Ms. Colle estimates 75,000 Canadians a year are now diagnosed with AMD and says “It is going to become a crisis of epic proportions within the next ten years.”

AMD, as with most causes of blindness, destroys tissues in the retina. A curved structure at the back of the eye, the retina is a multilayered lasagna of delicate cells that there was once little hope of replacing.

But embryonic stem cells can grow into all the body’s tissue types and, says Robert Lanza, chief scientific officer at Advanced Cell Technology, the company poised to test their therapeutic value in Stargardt patients, they particularly “want to assemble into eyes.”

“They start clumping together … you can see these miniature eyes,” he says.

One tissue type they make in abundance is called the retinal pigmented epithelium, or RPE cells for short. They form the retina’s dark, supportive under layer, and happen to be the first to degenerate in AMD, setting off a chain of destruction that kills other cells, including the crucial light-sensing neurons known as photoreceptors.

But with “one preparation” of embryonic stem cells, “you can grow up enough [RPE cells] to treat thousands of patients,” says Dr. Lanza, adding that his company plans to next seek FDA permission for a trial in AMD patients.

Yet only recently did scientists discover that the retina of an adult also contains versatile stem cells. For years experts believed that unlike fish and frogs, mammals had no capacity to rally replacement cells in the retina once they were damaged. But in 2000, Prof. van der Kooy’s group published a landmark paper proving stem cells exist in the retinas of adult mice, just as stem cells were surprisingly discovered to exist in the adult brain.

What’s more, says Prof. van der Kooy, a single human eye may harbour as many as 10,000 retinal stem cells, “regardless of age – whether the person is six days old or 80 years old.”

In the human eye, which stops growing around age two, retinal stem cells lie dormant. But cultured in a lab dish, they can regenerate faster than rabbits. “From a single retinal stem cell, you can generate several million cells,” says Prof. van der Kooy, and each one can make all seven cell types within the retina, including photoreceptors. In the later stages of AMD, and other less common eye diseases, photoreceptors die off, leaving dark blotches in the field of vision.

In a deal with the Eye Bank of Canada, the Toronto team is growing them by the batch, harvesting retinal stem cells from eye donors within 24 hours of their death. The cells are then chemically coaxed to become photoreceptors and injected into the retinas of their specially bred blind mice.

Researchers had to invent a special gel to spread the cells across the surface of the retina. Even still, only 5 per cent survive, which is why, says Prof. van der Kooy, the mice have only partial sight restored. “We have to scale it up,” he says. Work is under way to add nutrients to the gel to keep more cells alive and coax them to connect with other photoreceptors.

Tom Reh, a long-time stem cell and vision researcher at Seattle’s University of Washington, says photoreceptors have not been prime targets for regeneration partly because they are hard to grow, the human eye needs so many millions of them, and they will benefit fewer patients than RPE cells.

Yet implanting RPE cells “may be more prone to generating an immune response because they sit right next to the blood supply, whereas photoreceptors sit behind the blood-retinal barrier.

Prof. Reh has also grown photoreceptors from embryonic stem cells, and restored some sight to blinded mice. He says everyone is trying different approaches and predicts a long road of “a lot of small steps” to come.

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