New transplantation technology has restored the mice's eyesight

Japanese researchers from the RIKEN Center for Developmental Biology, working under the leadership of Masayo Takahashi, demonstrated in experiments on mice that retinal transplants grown from induced pluripotent stem cells (iPSCs) can restore visual function.

Retinal degeneration is primarily a hereditary disease characterized by the death of photoreceptors – the light–sensitive neurons of the eye - ultimately leading to complete blindness. Until today, researchers have repeatedly attempted to cure the disease with the help of retinal transplantation, while in some cases photoreceptor transplantation, even without significant integration into the recipient's tissue, allowed to restore the function of the retina. However, until now, no one has been able to achieve successful functional integration of transplanted photoreceptors with recipient cells and the transmission of visual signals generated by them to the retina and brain.

The authors studied this problem in a mouse model of the last stage of the disease, in which the outer nuclear layer of the retina is completely destroyed. This factor is very important, since in clinical practice such therapy is most likely to be used precisely in cases when all photoreceptors have already died and the neurons in contact with them do not receive any signals.

In earlier work, they demonstrated the structural integrity of three-dimensional retinal layers grown from mouse embryonic cells. According to the researchers, this is a key point, since the transplantation of retinal tissue instead of individual photoreceptors makes it possible to form a more mature organized morphology that provides a better response to light signals.

To assess the success of transplantation, the authors implanted several modifications of retinal layers in animals with simulated retinal degeneration. They used a fluorescent protein to label the end sections of photoreceptors with which these cells were supposed to connect to neurons – bipolar cells of the retina – and, eventually, to the brain. Another fluorescent protein was used to label bipolar retinal cells, which allowed us to demonstrate the formation of contact between the labeled cells of the transplant and the recipient.

Three-dimensional image of the contacts between the bipolar cells of the recipient (green) and the outer nuclear layer of the graft cells (red). The cells of the transplanted area of the retina are colored blue.

To assess the ability of mice to see light, scientists applied a behavioral training task. Mice with normal vision are trained to associate sound and light signals with various events in the same way as Pavlov's famous dog associated food with the sound of a bell. At the same time, animals without a photoreceptor layer of the retina did not have the ability to form associations between events and light stimuli before surgery, but acquired it after transplantation. This means that the new retinal cells not only reacted to light, but also transmitted the relevant information to the brain, providing the animals with the opportunity to learn.

The authors are going to conduct additional research on the transplantation of retinal tissue grown from human induced pluripotent stem cells to animals. After that, they plan to move on to clinical studies of the method, since only this approach will determine how many new contacts between photoreceptors and bipolar retinal cells are needed to restore vision.

Despite the promising results, they warn that today the therapy is under development and it is very premature to expect the restoration of full vision with its help. At the initial stage, it will return to the eye the ability to register light, after which it may be possible to obtain more impressive results.

Article by Michiko Mandai et al. iPSC-derived retinal transplants improve vision in rd1 end-stage retinal degeneration mice published in the journal Stem Cell Reports.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the RIKEN Center for Developmental Biology: New transplant technique restores vision in mice.

13.01.2017