Transplanted human stem cells successfully repaired macular holes in monkey models of the disorder. This is according to a new study from researchers at the Center for Biosystems Dynamics Research at RIKEN, Kobe City Eye Hospital, and colleagues at other institutions. Their findings are described in a paper published in Stem Cell Reports titled, “Transplantation of human pluripotent stem cell-derived retinal sheet in a primate model of macular hole.”
Macular holes are tiny gaps that form in the eye, specifically the macula which is located in the central part of the retina, that cause blurred or distorted vision. Surgical approaches are effective in about 90% of cases but refractory cases are still a challenge as is the management of recurrent macular holes post surgery. Additionally, retinal transplantations can be an effective form of treatment but visual improvement is limited and there can be defects in the peripheral visual field.
To address these issues, the scientists in this study assess whether transplanting human embryonic stem-cell-derived retinal organoid sheets could be an effective form of treatment. The experiments in Japanese macaques showed that transplanting human embryonic stem cell organoid sheets resulted in successful closure of the holes. They saw evidence of graft survival and maturation as well as the development of light-detecting retinal cells including rods and cones. The monkeys also showed evidence of improved eye fixation and responses to light.
These findings are promising and point to a new path to treatment for macular holes. “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,” said Michiko Mandai, MD, PhD, the study’s senior author. “Our results suggest that this method could become a practical, safe, and effective treatment option with minimal invasive risks, particularly for difficult macular hole cases.”
To be clear, there is still much to be done to test and validate stem cells as a treatment approach for this condition. The scientists noted that the test subjects showed mild transplantation rejection. This could be controlled with steroid injections but it is possible that the rejection “limited the functional integration of the transplanted tissue,” Mandai noted. Furthermore, “this was a single-case result for one eye, and the model did not exactly replicate the pathology of human refractory macular holes.”
Additional studies are needed to assess the protective effect of the treatment for host retinal cells as well as to understand how the cell composition of the graft influences visual function. For their next steps, Mandai and her team plan to study whether a form of synaptic communication could be established between the graft and host cells.