AsianScientist (Jan. 18, 2017) – Retinal transplants derived from induced pluripotent stem cells (iPSCs) have helped to restore vision in mice. These findings, published in Stem Cell Reports, show that neurons in the implanted retinal sheets integrate well with the host, respond to light, and send their signals to the brain as judged by behavioral experiments.
Retinal degeneration is a hereditary disease characterized by the death of photoreceptors—the light-sensitive neurons in the eye—which eventually leads to blindness. While many have attempted to treat the disease through retinal transplants, and some have shown that transplanting graft photoreceptors to the host without substantial integration can rescue retinal function, no one has conclusively succeeded in transplanting photoreceptors that functionally connect to host cells and send visual signals to the host retina and brain.
Now, a team led by Professor Masayo Takahashi has shown that 3D retinal sheets derived from mouse embryonic stem cells develop normal structure connectivity.
“Using this method was a key point,” explained study first author Dr. Michiko Mandai. “Transplanting retinal tissue instead of simply using photoreceptor cells allowed the development of more mature, organized morphology, which likely led to better responses to light.”
To assess the success of the transplantations, the team integrated some modifications to the retinal sheets and the model mice. They used a fluorescent protein to label the ends of the photoreceptors, which is where they would connect to the host neurons—the bipolar retinal cells—and ultimately the brain.
After labeling the host retinal bipolar cells with a different fluorescent protein, they found that the labeled cell terminals from the graft did indeed make contact with the cells labeled in the host, indicating that the newly grown photoreceptors naturally connected themselves to the bipolar cells in the model mice.
Mice with normal vision can learn to associate sounds or light with different events. While the model mice who lacked a photoreceptor layer in their retinas could not learn to associate anything with light before surgery, they could after the transplant, provided that a substantial amount of the transplant was located in the correct place. This means that not only did the new cells in the retina respond to light, but the information traveled to the brain and could be used normally to learn.
“These results are a proof of concept for using iPSC-derived retinal tissue to treat retinal degeneration,” said Mandai. “We are planning to proceed to clinical trials in humans after a few more necessary studies using human iPSC-derived retinal tissue in animals. Clinical trials are the only way to determine how many new connections are needed for a person to be able to ‘see’ again.”
Although the results are promising, Mandai cautions that for now this therapy is at the developmental stage.
“We cannot expect to restore practical vision at the moment,” she explained. “We will start from seeing a simple light, then possibly move on to larger figures in the next stage.”
The article can be found at: Mandai et al. (2017) iPSC-derived Retinal Transplants Improve Vision in rd1 End-stage Retinal Degeneration Mice.
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Source: RIKEN; Photo: Brian Valentine/Flickr/CC.
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