An international research team led by Columbia University Medical Center successfully used mouse embryonic stem cells to replace diseased retinal cells and restore sight in a mouse model of retinitis pigmentosa. This strategy could potentially become a new treatment for retinitis pigmentosa, a leading cause of blindness that affects approximately one in 3,000 to 4,000 people, or 1.5 million people worldwide.
The study appears online ahead of print in the journal Transplantation (March 27, 2010 print issue).
Specialized retinal cells called the retinal pigment epithelium maintain vision. Retinitis pigmentosa results from the death of retinal cells on the periphery of the retina, leading to "tunnel vision," where the field of vision is narrowed considerably and everything outside the "tunnel" appears blurred or wavy.
"This research is promising because we successfully turned stem cells into retinal cells, and these retinal cells restored vision in a mouse model of retinitis pigmentosa," said Stephen Tsang, M.D., Ph.D., assistant professor of ophthalmology, pathology and cell biology, Columbia University Medical Center, and lead author of the paper. "The transplanted cells not only looked like retinal cells, but they functioned like them, too."
In Dr. Tsang's study, sight was restored in one-fourth of the mice that received the stem cells. However, complications of benign tumors and retinal detachments were seen in some of the mice, so Dr. Tsang and colleagues will optimize techniques to decrease the incidence of these complications in human embryonic stem cells before testing in human patients can begin.
"Once the complication issues are addressed, we believe this technique could become a new therapeutic approach for not only retinitis pigmentosa, but age-related macular degeneration, Stargardt disease, and other forms of retinal disease that also feature loss of retinal cells," said Dr. Tsang.
In age-related macular degeneration, retinal cells in the center of the retina degenerate and cause the center part of vision to become blurry or wavy. In 2010, macular degeneration is prevalent in nine million Americans and its incidence is expected to double by 2020. It is estimated that 30 percent of the population will have some form of macular degeneration by the time they reach the age of 75.
Replacement of damaged retinal cells in patients with macular degeneration is currently offered in some hospitals, but the therapy is limited by a shortage of donor retinal pigment epithelium cells. By using stem cells and turning them into retinal pigment epithelium cells, the supply is virtually unlimited.
Similar approaches to macular degeneration have demonstrated efficacy in other rodent models, but since these models are of rare, unique pathophysiologies of retinal degeneration, they may not be generalizable to most human forms of retinal degeneration, e.g., age-related macular degeneration, retinitis pigmentosa or Stargardt disease.
"It's a good thing that more models are being tried, as this shows there may be real potential for stem cells to treat different causes of the loss of retinal pigment epithelium in humans," said Dr. Tsang.
The research methods used in this study were developed by Columbia researchers, past and present, including:
"I am fortunate that this diverse expertise exists at the same university -- Columbia is one of the few places in the world where this research could be conducted," said Dr. Tsang. "And our multidisciplinary approach to basic science research is unique."
This research was supported by grants from the National Institutes of Health, Research to Prevent Blindness, New York, NY, the Foundation Fighting Blindness, the Dennis W. Jahnigen Career Development Scholars Award Program of American Geriatics Society, the Schneeweiss Stargardt Fund, and Professor Gertrude Neumark Rothschild.
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