Successful integration of iPSC-derived human photoreceptor cells into the retina after transplantation and restoration of photoreceptor ability in mice

Eyes are the windows to the soul, but not everyone can have a bright pair of pupils. In the vision of blind patients, the world is not colorful, and blackness or nothingness is all they see in front of them.

According to research, the human brain absorbs external information primarily through the five senses- sight, hearing, smell, touch, and taste, with vision receiving at least 80% of total external information. As a result, blindness is a very dreadful and terrible thing for individuals, causing not only a lot of inconvenience, but also a severe blow to the blind person’s spiritual beliefs.

Blindness treatment has always been challenging, and there has been a dearth of effective clinical treatments for blindness. Photoreceptor cell transplantation is a promising technique for restoring vision in people with blinding conditions.

Researchers from the University of Dresden, Germany, recently published a study in the Journal of Clinical Investigation entitled: Transplanted human cones incorporate into retina and function in a murine cone degeneration model.

The team developed a large number of iPSC-based human photoreceptor cells in vitro and then transplanted them into mouse retinas. The results demonstrated that these human photoreceptor cells were able to integrate significantly into the deteriorated mouse retinas and restore light perception in the visually impaired mice.

According to Professor Marius Ader, who conducted the study, “this is the first time transplanted photoreceptor cells have been incorporated into the retina on such a vast scale, signifying a new milestone in the treatment of blindness disease by photoreceptor cell transplantation.”

The researchers made many adjustments to improve the integration effectiveness of photoreceptors after transplantation and discovered that the “age” of the transplanted photoreceptors was a critical factor in integration efficiency. The integration efficiency of transplanted photoreceptors into the retina was dramatically lowered for both “younger” and “older” photoreceptors. They also discovered that it took up to 6 months for these photoreceptors to integrate into the retina before they could develop an interactive network with other retinal cells and achieve integration.

The research team first used human-induced pluripotent stem cells (iPSCs) in culture dishes to grow retinal-like organs in laboratory dishes, which were harvested and used for transplantation when these retinal-like organs reached the appropriate stage of development.

Obtaining purer photoreceptor cells was a challenge in this study, and to address this problem, the team developed a new stem cell line using the piggyBac transposon system to generate hiPSC cell lines carrying green fluorescent protein (GFP) under the control of the cone-specific mouse cone repressor protein (mCar) promoter. The incorporation of these tags enabled the effective extraction of targeted photoreceptor cells from grown retinal-like organs while preserving cell function. Furthermore, this induced pluripotent stem cell line provided an almost limitless source of photoreceptor cells, setting the groundwork for future large-scale therapeutic applications.

Following that, the researchers studied mice with partially degenerated retinas with damaged cone cells and normal rod cells of the two types of photoreceptors. Cone cells mostly experienced bright light, color vision, and strong light, whereas rod cells primarily perceived low light, dark vision, and no color vision.

The researchers transplanted cultured and purified photoreceptor cells into mice with damaged cone cells, and the results showed that the transplanted photoreceptor cells successfully integrated into the mouse retina and developed into functional photoreceptors, as well as transmitting signals to downstream retinal nerve cells normally, allowing the mice to regain their photoreceptor ability.

The preclinical study, according to Professor Marius Ader, revealed that transplanting photoreceptors in patients with blinding disease before they have entirely degraded is a viable strategy to restore vision.