End-stage retinal degeneration includes conditions such as age-related macular degeneration and retinitis pigmentosais. It is the most common cause of irreversible vision loss and blindness in older adults.
In these types of conditions, sight gradually worsens as the nuclear layer of light-sensitive photoreceptor cells in the eyes is degraded.
As the population of the United States begins to live longer, the prevalence of retinal degeneration slowly increases.
For example, the number of individuals affected by age-related macular degeneration between 2000-2010 jumped from 1.75 million to 2.07 million.
Although degeneration of the outer retinal layer cannot be reversed, one potential strategy that might eventually help to restore vision is cell replacement.
Stem cell-derived retinal tissue
Cell replacement technology is in its infancy but shows real promise. A group of scientists from the RIKEN Center for Developmental Biology in Japan, led by Masayo Takahashi and Michiko Mandai, is heavily involved in this innovative field of study.
In earlier research, the researchers transplanted stem cell-derived retinal tissues into animals with end-stage retinal degeneration. They found that this tissue could be coerced into forming structured outer nuclear layers that included mature photoreceptors.
While this marked a huge step forward, the researchers did not demonstrate whether the transplantation of cells could restore vision. Their latest study set out to fill this gap in the study.
The first stage of the research involved reprogramming adult mouse skin cells to behave in a similar way to embryonic stem cells. These cell types are called induced pluripotent stem cells (iPSCs). Next, the iPSCs were converted into retinal tissue.
Once the iPSCs had been implanted into mice with end-stage retinal degeneration, they developed and formed photoreceptors. In turn, these photoreceptors directly contacted neighbouring cells within the retina.
“We showed the establishment of host-graft synapses in a direct and confirmative way. 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.
Testing for restored vision
To test whether the animals’ vision had been restored, the researchers placed the mice in cages consisting of two rooms. The floor of one of the rooms was electrified at random points in time. Preceding each electric shock, the team flashed a warning light. To avoid the shock, the mouse had to see the light flash and move to the adjoining room.
Going beyond expectations, the procedure managed to restore sight in almost half of the mice with end-stage retinal degeneration. Such significant success was due to the researchers’ choice of cells. Previous work has used retinal cells rather than the differential retinal tissue used in this study. Takahashi explains:
“The photoreceptors in the 3-D structure can develop to form more mature, organized morphology, and therefore may respond better to light. From our data, the post-transplantation retina can respond to light already at 1 month in mice, but since the human retina takes a longer time to mature, it may take 5-6 months for the transplanted retina to start responding to light.”
Takahashi and colleagues are now extending their investigation to make these findings more applicable to patients. They are already investigating whether human iPSC-derived retinal tissue can restore visual function in animals with end-stage retinal degeneration.
There is still much work to be done, as Takahashi is well aware: “It is still a developing-stage therapy, and one cannot expect to restore practical vision at the moment. We will start from the stage of seeing a light or large figure, but hope to restore more substantial vision in the future.”
As the team continues to test new avenues for iPSC-derived retinal tissue, the ability to restore lost sight inches closer.
Source: Medical News Today