Stem cells restore vision in blind mice

Japanese scientists from the RIKEN Center for Developmental Biology report a method of treatment of degenerative changes of the retina at the terminal stage. Derived from mouse tissue induced pluripotent stem cells (IPSCs) created cell-cell communication with the environment, responded to stimulation by light after transplantation into the host retina and restore visual function in mice with end-stage retinal degeneration. The researchers report in an article published on 10 January 2017 in Stem Cell Reports.

End-stage degeneration of the retina is the main cause of irreversible vision loss and blindness in older people. As a rule, patients with such diseases as retinitis pigmentosa and age-related macular degeneration, lose their vision because of damage to the outer nuclear (granular) layer of light-sensitive photoreceptor cells of the eye. Currently, the retinal degeneration end-stage is not treated. The only available therapies have limited ability to prevent the progression of vision loss.

One of the modern strategies to restore vision in patients who have lost vision because of retinal degeneration, is based on cell transplantation.

A team of scientists led by Masayo Takahashi in previous studies showed that the retinal tissue derived from stem cells, after transplantation to animals with end-stage retinal degeneration could develop to form structured outer nuclear layers consisting of mature photoreceptors. However, now it was not clear whether the transplantation of these cells to restore visual function.

In a new study by Takahashi together with Michiko Mandai, the first author of the work, decided to study the matter. To do this, they first reprogrammed skin cells obtained from adult mice, and then turned established IPSC in the retinal tissue. After the transplantation into mice with end-stage degeneration of the retina, the tissue formed photoreceptors, which created a direct communications with adjacent cells.

In addition, almost all grafts showed some response to light stimulation. The success of the results is that was used the differentiated retinal tissue, but not cells of the retina, as in most the studies in this field.

“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.”

It is noteworthy that this therapeutic strategy to restore the vision of almost half of the mice with end-stage retinal degeneration. Mice were placed in a box consisting of two chambers, which independently delivered electric shocks on the floor. They were able to use a light warning signal to avoid the shocks, and ran across to the next chamber. Thus, scientists have noted a partial recovery of vision in some mice.

“We showed the establishment of host-graft synapses in a direct and confirmative way,” Mandai says. “No one has really shown transplanted stem cell-derived retinal cells responding to light in a straightforward approach as presented in this study, and we collected data to support that the signal is transmitted to host cells that send signals to the brain.”

In order to make the study results applicable to patients, scientists are now exploring the possibility of restoring vision in animals with end-stage retinal degeneration with retina derived from human induced pluripotent stem cells.

If the experiment is successful, the researchers intend to test the security of this protocol, in particular, the graft-versus-host reaction. They will also look at ways to enhance the ability of transplanted photoreceptors to integrate with the host retinal tissue, with the ultimate goal of moving to clinical trials in humans.

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