A promising method treating blindness is implanting healthy light-sensitive cells into weak eyes. But these cell therapies, which have been in development for at least three decades, often fail because the implanted cells die quickly or fail to incorporate into the eye. But new stem cell research could potentially remove these obstacles.
What’s new – Experiments with human and dog stem cells reveal that a cocktail of drugs that suppress the immune system could help implanted cells survive for months. In fact, the implanted cells even began to integrate with the eyes, according to a new study published in the journal Stem Cell Reports.
The scientists injected immunosuppressed dogs with advanced stages of hereditary retinal degeneration with photoreceptor cell precursors obtained from human stem cells. They found that the immature cells became fully developed photoreceptors and began to form connections with the dogs’ neurons. The research offers a critical first step toward using stem cell therapies to treat eye conditions, including hereditary forms of blindness.
HERE IS THE BACKGROUND – Genetic cases of blindness are often the result of problems with the light-sensitive rod and cone cells in the retina, the tissue that lines the inner eyeball. Scientists have had great success treating some genetic eye conditions using gene therapies, which involve injecting working versions of malfunctioning genes into the eye’s photoreceptor cells. But the genes responsible for many genetic cases of blindness remain unknown.
In turn, various forms of genetic blindness have no gene therapy and, indeed, no therapeutic option. And for some people it’s already too late: their condition has progressed so far that no photoreceptor cells remain intact, so gene therapy would have no effect anyway. Instead, regenerative therapies to replace diseased photoreceptors with functional cells could offer another avenue to reverse blindness.
How they did it? In the new study, the researchers dosed human stem cells with chemicals that coaxed them to form the precursors of photoreceptor cells. To help track the positions of these cells over time, the stem cells were genetically modified to generate fluorescent proteins.
The scientists then injected them into the retinas of seven dogs with normal vision and three with advanced stages of inherited retinal degeneration. In animals, these immature cells matured into photoreceptors.
When the stem cells were injected into the normally sighted dogs, their retinas were still intact and thus served as physical barriers that prevented the implanted cells from connecting with neurons in the eyes. But in dogs with retinal degeneration (for which the treatment is directed), the injected cells migrated much better to the retina.
Since the canines’ immune system would likely recognize the transplanted human cells as foreign entities and attack them, the researchers administered some immunosuppressive drugs.
As expected, the number of injected cells decreased substantially in the canines that did not receive the drug cocktail, while the number of cells decreased but then remained constant in the dogs that received the drugs. Cells from immunosuppressed dogs survived up to five months after injection. The researchers also detected signs of implanted cells connecting with neurons in the pups’ eyes.
Why does it matter? The discovery that human photoreceptor precursor cells could survive and mature into photoreceptor cells after being transplanted into an adult canine retina suggests that it is possible to regenerate a specific layer of the retina, the one containing the rod and cone photoreceptors, in an adult eye.
“This gives hope of being able to treat patients even in adulthood,” says Beltrán.
Importantly, the dogs used in this study also provide a better picture of how the same therapy might work in humans. The study’s lead author, William Beltran, a veterinary ophthalmologist and vision scientist at the University of Pennsylvania, says Reverse that dogs are good models for humans in this case for several reasons, apparently making translating the research to human bodies later on a simpler task.
For one, large animal models with human-sized eyes allow scientists to develop the same surgical approaches that can be used in people.
Dogs also receive doses of therapy similar to those that would likely be used in people, and can experience some of the same immune reactions that we do.
WHATS NEXT – In the future, the researchers will continue to refine their technique and eventually test whether dogs experience better vision due to the implanted cells.
It’s still unclear why some implanted cells died a few days after the transplant, even when the dogs were given immunosuppressive drugs. The team is investigating this process in hopes that they can try to improve graft survival, says Beltrán.
Still, future cell therapies for retinal degeneration may require immunosuppressive drugs if the donor’s cells are not genetically identical to the recipient’s. The best approach to prevent adverse immune reactions without using immunosuppressive drugs would be to inject photoreceptors derived from the patient’s stem cells after genetic defects have been corrected, says Beltrán.
Treatments for blindness may soon join the rapidly expanding and extremely expensive category of personalized medicine.