The gift of sight

Microscopic ‘gifts’ may be helping those who receive stem cell transplants in order to restore their damaged retina to see again.

Stem cell transplants in human patients are still in the very early stages of development, but new research has thrown into question exactly how the donated stem cells help the retina to recover from disease.

University College London researcher, Professor Rachael Pearson, told OT that scientists had thought that the transplanted donor cells migrated into the retinal layers and began to function, replacing the dying host cells.

However, her latest research, funded by the Medical Research Council and Fight for Sight, suggests it may be more complicated than this.

Using mice, Professor Pearson took donated photoreceptor cells that were adapted to produce a green fluorescent colour from a male mouse, meaning the cells all contained a Y chromosome.

The researchers then added these cells to the retina in a female mouse – which lacks any Y chromosomes and with photoreceptors that were adapted to glow red.

Professor Pearson explained that while a few green, donor cells integrated into the retina, this was rare. Instead, a large number of red, host cells started to create proteins that glowed the same green as the donor cells, according to the paper published in the journal Nature Communications.

The researchers ruled out classic cell fusion as none of the female host cells had a Y chromosome within them. Instead, the group concluded that the green, donor cells are transferring important cellular material to the ailing red cells.

“We were very surprised. It wasn’t what we was expected. It made us re-think what we thought we knew about the underlying mechanisms,” she emphasised.

The donor cells may be gifting this material through a cellular “care package.” But at this stage, this remained a theory, Professor Pearson highlighted.

“We don’t know what the cellular mechanism behind this is yet. However, it appears to be sufficient to rescue visual function,” she said.

Professor Pearson’s current research aims to answer this question, and look beyond the eyes of mice, she highlighted, adding: “We don’t know if it occurs between human cells.”

However, there is a chance that this discovery could one day be used as a therapy to restore the health of dying photoreceptor cells in patients.

“This knowledge may have therapeutic benefits. If the material is being transferred in packages, it is possible that we could replicate these and introduce these into the eye,” she envisioned.

The finding has implications for stem cell transplants in patients in the late stages of retinal disease, when material transfer cannot occur as there are no photoreceptors left to receive the donor material.

Professor Pearson’s group is also investigating transplants in this specific scenario.

She outlined that: “Donor cells transplanted into these eyes appear to form new connections with the remaining retina and can drive visual function.”

Fight for Sight research director, Dolores Conroy, highlighted that: “Some degenerative retinal conditions are currently untreatable as the underlying cause is not yet known.

“For these conditions in particular, and if we can determine the mechanism, material transfer may offer a way to offer the degenerating retina a means of repair that can rescue vision to some degree,” Ms Conroy concluded.