Hole in monkey’s retina fixed with patch derived from human stem cells

Scientists have achieved a remarkable success in retinal transplantation. They have fixed a hole in a monkey’s retina with a patch derived from human stem cells.

Researchers used a non-human primate model and evaluated whether human embryonic stem cell-derived retinal organoid (RO) sheet transplantation can be an effective option for treating macular hole (MH).

After transplantation, MH was successfully closed by continuous filling of the MH space with the RO sheet, resulting in improved visual function, although no host-graft synaptic connections were confirmed.

The study maintains that mild xeno-transplantation rejection was controlled by additional focal steroid injections and rod/cone photoreceptors developed in the graft.

Stem cell-derived RO sheet could be a practical option

“Overall, our findings suggest pluripotent stem cell-derived RO sheet transplantation as a practical option for refractory MH treatment,” they said.

Macular holes, which can cause distorted or blurred vision, are small gaps that form in the macula — the central part of the retina in the eye.

Dr. Michiko Mandai, of Kobe City Eye Hospital in Japan, stated that the results suggest that this method could become a practical, safe and effective treatment option with minimal invasive risks, particularly for difficult macular hole cases.

“We confirmed for the first time in a non-human primate model that embryonic stem-derived retinal organoid sheet transplantation facilitates the closure of macular holes,” added Mandai.

Although advances in vitreoretinal surgical techniques achieve more than 90% MH closure rate, refractory cases still exist.

For such cases, autologous retinal transplantation is an optional therapy showing good anatomic success, but visual improvement is limited and peripheral visual field defects are inevitable after graft harvesting, claimed researchers in the study .

Eye fixation test

Researchers maintained that during the eye fixation test, the monkey was seated in a primate chair in dim light. Before this test, the monkey was under step-by-step water restriction for 1 week.

“In conclusion, PSC-derived retinal transplantation contributed to MH closure with continuously integrated tissue containing rod, S-, and L/M-cone PRs and improved visual function,” said researchers.

This approach is claimed to simplify the ART procedure with advantages of no need for harvesting the peripheral retina, preparation of different sizes of sheets, including the one for a large MH, and inclusion of cone PR precursor cells in the graft.

Researchers maintained that further studies are needed to validate the functional advantage of the PSC-derived retina including the synaptic connectivity with and protective effect for host retinal cells.

Mandai stated that with macular hole, the improvement in vision arises from the eye recovering its structural organization and function after that hole is closed up.

“The mild rejection may have limited the functional integration of the transplanted tissue. Additionally, this was a single-case result for one eye, and the model did not exactly replicate the pathology of human refractory macular holes. However, the findings suggest that the surgical technique is feasible for human macular holes,” added Mandai.

The study published in the journal Stem Cell Reports .