Blind Mice Get Experimental Stem Cell Treatment For Blindness

April Flowers for – Your Universe Online

Columbia University ophthalmologists and stem cell researchers have developed an experimental treatment for blindness using the patient’s skin cells, which has improved the vision of blind mice in testing.

The findings of this research, published online in the journal Molecular Medicine, suggest that induced pluripotent stem cells (iPS) could soon be used to improve vision in people with macular degeneration and other eye retina diseases. iPS cells are derived from adult human skin cells but have embryonic qualities.

“With eye diseases, I think we´re getting close to a scenario where a patient´s own skin cells are used to replace retina cells destroyed by disease or degeneration,” says Stephen Tsang, MD, PhD, associate professor of ophthalmology and pathology & cell biology. “It´s often said that iPS transplantation will be important in the practice of medicine in some distant future, but our paper suggests the future is almost here.”

Scientists were very excited by the advent of human iPS cells when they were discovered in 2007, as they provide a way to avoid the ethical complications of embryonic stem cells. Another advantage is that the iPS cells are created from the patient’s own skin, eliminating the need for anti-rejection medications. Like the ethically challenged embryonic cells, iPS cells can develop into any type of cell. To-date, no iPS cells have been implanted into people, but many ophthalmologists say that the eye would prove to be ideal testing ground for iPS therapies.

“The eye is a transparent and accessible part of the central nervous system, and that´s a big advantage. We can put cells into the eye and monitor them every day with routine non-invasive clinical exams,” Tsang said. “And in the event of serious complications, removing the eye is not a life-threatening event.”

Professor Tsang is running a new preclinical iPS study using human iPS cells derived from the skin cells of a 53-year-old donor. The cells were first transformed with a cocktail of growth factors into cells in the retina that lie underneath the eye’s light-sensing cells.

Retina cells nourish the light-sensing cells and protect the fragile cells from excess light, heat and cellular debris. In macular degeneration and retinitis pigmentosa, retina cells die, which allows the photoreceptor cells to degenerate causing the patient to lose their vision. It is estimated that 30 percent of people will have some form of macular degeneration by the time they are 75 years old, as it is the leading cause of vision loss in the elderly. Currently, it affects 7 million Americans and that is expected to double by 2020.

The Columbia research team injected the iPS-derived retina cells into the right eyes of 34 mice that had a genetic mutation that caused their retina cells to degenerate. In many of the mice, the iPS cells assimilated into the retina without disruption and functioned as normal retina cells well into the animal’s old age.  Mice in the control group, who received injections of saline or inactive cells, showed no improvement in retina tests.

“Our findings provide the first evidence of life-long neuronal recovery in a preclinical model of retinal degeneration, using stem cell transplant, with vision improvement persisting through the lifespan,” Tsang says. “And importantly, we saw no tumors in any of the mice, which should allay one of the biggest fears people have about stem cell transplants: that they will generate tumors.”

They hope to begin a clinical trial for macular degeneration patients in the next three years, but first need to complete more preclinical testing in animal models.

A similar trial testing retina cells derived from embryonic cells rather than iPS has seen encouraging results. A paper published earlier this year reported that the stem cells are safe and have the potential to improve the vision of two patients with macular degeneration.

“These results are encouraging, but iPS cells could be a more attractive option than embryonic stem cells,” Tsang says, “because patients may not need drugs to prevent rejection of the transplanted cells.”

Whichever type of stem cell works better, the prospect to reverse and prevent macular degeneration is encouraging.

“We have a good idea which patients will eventually lose their vision. In the early stages of macular degeneration we can tell by looking in the eye, and new genetic tests can now predict vision loss with 70 percent accuracy even before those signs emerge,” Tsang says. “If the therapy is safe, we could intervene very early to prevent much vision loss.”