Human Stem Cell-Derived Retinal Organoid Sheets Close Macular Holes

Researchers reported in the journal Stem Cell Reports that retinal holes in a monkey model were successfully healed by transplanting human stem cells. Following transplantation, retinal tissue was continuously added to the macular holes to seal them.

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. 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.”

Michiko Mandai, Study Senior Author, Kobe City Eye Hospital

Macular holes are tiny holes that develop in the macula, the retina's center region in the eye. They may result in distorted or blurry center vision, which makes it challenging to read, drive, or see small details.

Surgical procedures have improved over the last 10 years to reach closure rates of 90%, although refractory cases remain a challenge. After surgery, managing recurring macular holes presents additional difficulties.

Cell-based therapy is a promising approach to restore vision in retinal degenerative illnesses. While retinal transplantation has demonstrated remarkable anatomic success, peripheral vision field abnormalities are unavoidable, and visual recovery is limited.

Mandai and colleagues assessed in the new study whether transplanting retinal organoid sheets generated from human embryonic stem cells may help them overcome these obstacles. After the retinal tissue was transplanted, grafts survived and matured, and photoreceptors, which include rods and cones that detect light in the retina, developed. Further tests showed improvements in the responses to light and ocular fixation.

A few limitations were noted by the researchers, including a slight transplant rejection that they managed with steroid injections.

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.”

Michiko Mandai, Study Senior Author, Kobe City Eye Hospital

The benefit of the stem cell-derived retina, particularly its ability to shield host retinal cells, will need to be further investigated, according to the scientists.

Further investigation is required to comprehend how the graft's cell makeup affects visual function. For their part, the researchers want to study whether some type of synaptic connectivity may be created between the host and graft over a longer time of observation.