Researchers in Japan have demonstrated that photoreceptor cell grafts made from induced pluripotent stem cells (iPSCs) can respond to light and successfully transmit signals to neighboring neurons cells after implantation in the retina in a mouse model of end-stage retinal degeneration.
The study, published Jan. 10 in Stem Cell Reports, represents the first verified instance of cells from a retinal transplant forming functional synapses with the host’s bipolar cells. These intermediary neurons then pass the signal to retinal ganglion cells (RGCs) which in turn, transmit the light information to the brain.
Nearly half of the mice that received iPSC retinal tissue showed some light responsive behavior during tests performed 1.4 to 4 months after implantation, indicating that the grafts not only show potential to restore vision but they may also survive long-term in the host.
Previous studies showed that both human and mouse-derived embryonic stem cells (ESCs) and iPSCs could develop into a structured, layered tissue with mature photoreceptors nearly identical to the eye’s outer nuclear layer (ONL), but it was unknown until now whether the grafts could restore visual function.
Destruction of the ONL occurs in the pathogenesis of many diseases, and there is currently no approved treatment to restore the resulting vision loss.
"Our study provides a proof-of-concept for transplanting stem cell-derived retinal tissues to treat patients with advanced retinitis pigmentosa or age-related macular degeneration,” said study leader Masayo Takahashi, MD, PhD.
The authors are currently evaluating whether the same procedure could be successful using human iPSCs. If so, they hope to initiate a human clinical in approximately 2 years.
"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,” said Dr. Takahashi.