Researchers Cure Blind Mice by Transplanting Photoreceptors Derived from Stem Cells

A team of researchers managed to use human stem cells to restore the vision of blind laboratory mice. The team used photoreceptors derived from stem cells and suppressed the immune system long enough for the cells to become fully incorporated into the eyes. The details are in a paper that was just published in the journal Cell Stem Cell.

Photoreceptors are neurons—cells that transmit information through signal pathways, usually with the use of chemical or electrical signals. The cells are found in the retina and have become specialized to pass on information from the eyes to the full visual system. This process is what allows most animals to see and a loss of photoreceptors will eventually lead to blindness. Photoreceptors can be derived from stem cells, embryonic cells capable of growing into any kind of cell, but the eyes reject these new neurons. If researchers manage to suppress the immune system long enough to insert the replacement photoreceptors, they could potentially cure certain forms of blindness.

Scientists from the Buck Institute for Research on Aging first investigated a topic of debate in the scientific community—are the transplanted photoreceptors simply dying off over time or is the immune system actively removing them? In the past, researchers believed that the eyes weren’t affected by the body’s immune system in the same way other organs are monitored. After studying blind mice with transplanted photoreceptors, the team quickly concluded that the issue was the immune response. Although researchers had long believed that eyes were “immune privileged” and were not affected by the full immune system, this didn’t appear to be the case with transplanted photoreceptor cells.

Knowing this new information, the team began to investigate possible ways to suppress the immune system of the eye in order to replace degenerated photoreceptors. The team used immunodeficient IL2 receptor gamma mice, mice that are healthy but lack a receptor that typically triggers an immune response. Without this receptor, newly transplanted cells are not rejected and the team believed that this might include photoreceptors. Humans have the same receptor and it functions in roughly the same way, making this line of mice especially useful in research.

The team found that when mice lacked the IL2ry receptor, their eyes did not reject transplanted photoreceptor cells. The researchers then tried their technique with blind mice to see if the cells actually functioned after being accepted into the retina. During treatment, the mice could see and their eyes properly responded to light. Even after nine months, the photoreceptors were still functioning and the mice had essentially been “cured” of blindness. This shows that suppressing the immune system may allow for successful photoreceptor transplants.

The findings show that there is still hope for transplantation of photoreceptors derived from stem cells. The key is suppressing the immune system in a way that doesn’t harm the animals. The researchers plan to try an antibody to suppress the immune system, a technique used in organ transplants. Human trials are still far off but the team believes that restoring vision by replacing photoreceptors may be possible in the future.

REFERENCE

Zhu et al. Immunosuppression via Loss of IL2rγ Enhances Long-Term Functional Integration of hESC-Derived Photoreceptors in the Mouse Retina. Cell Stem Cell (2017).

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