Stem cell therapy restores sight to blind mice

A transplantation treatment based on stem cells has moved closer to being tested in humans with severe vision problems, after successful trials in mice.

The method, which was shown to restore visual function in half of mice with end-stage retinal degeneration, involved transplanting retinal tissue derived from mouse induced pluripotent stem cells (iPSCs) into the host retina.

In order to create the transplant tissue, researchers first genetically reprogrammed skin cells taken from adult mice to an embryonic stem cell-like state before converting these iPSCs into retinal tissue. When transplanted into mice with end-stage retinal degeneration, the iPSC-derived retinal tissue developed to form photoreceptors that established direct contact with neighbouring cells in the retina.

The treatment, developed by senior study author Masayo Takahashi and first author Michiko Mandai of the RIKEN Center for Developmental Biology, was able to restore vision in roughly half of the mice with end-stage retinal degeneration. The research team are now testing the ability to replicate the results using human-derived iPSC retinal tissue.

“It is still a developing-stage therapy, and one cannot expect to restore practical vision at the moment,” Takahashi cautioned. “We will start from the stage of seeing a light or large figure, but hope to restore more substantial vision in the future.”

End-stage retinal degeneration is a leading cause of irreversible vision loss and blindness in older individuals. There is currently no cure and therapies are limited in their capability to stop the progression of vision loss.

The therapy strategy used by the RIKEN team is that of cell replacement, a method that, until now, suffered from uncertainty as to whether transplantation of stem cell tissues could actually restore visual function.

The key to success found by the researchers was the use of differentiated retinal tissues as opposed to retinal cells, which have previously been the focus of field use for most researchers. In almost all of the retinas that were transplanted, the researchers found at least some measure of response to light stimulation.

“The photoreceptors in the 3D structure can develop to form more mature, organized morphology, and therefore may respond better to light,” Takahashi explains. “From our data, the post-transplantation retina can respond to light already at one month in mice, but since the human retina takes a longer time to mature, it may take five to six months for the transplanted retina to start responding to light.”

Although simple light perception isn’t full restoration of sight, it is indicative of the possibilities of the treatment and shows that visual functions can be restored.

Takahashi’s acknowledgement of the increased complexity of human cells requires bearing in mind; it will not be a simple switchover from mice to human patients. However, if their new experiments into human-derived tissues prove successful, it may not be long before work can begin transferring this restorative success to clinical trials.

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