A. Scanning laser ophthalmoscopy (SLO) image: White arrows indicate the incision for transplantation of the retinal organoid sheet, and the dotted line indicates the transplantation area. The green line indicates the spectral-domain OCT (SD-OCT) scan path.
B. SD-OCT image of the transplantation site. A cross-sectional view highlighting structural changes after transplantation.
C. Adaptive optics OCT (AO-OCT) images of the same site provide a high-resolution view detailing the outer plexiform layer (OPL) like line (arrowheads) and possible arrangement of the photoreceptor cells.
D. Magnified AO-OCT image showing a detailed view of the rosette-like arrangement of the photoreceptor cells.
E. Magnified AO-OCT image with color emphasis showing detailed photoreceptor structures (green) and their outer segments (yellow), illustrating the intricate architecture of the graft.
F. Maturation of human iPSC-derived retinas in a monkey model of retinitis pigmentosa with laser photoreceptor ablation. A row of recoverin-positive transplanted photoreceptors are aligned with INL in the outer nuclear layer (ONL)-ablated region, suggesting a successful graft integration.
G. Rhodopsin-positive transplanted photoreceptors show different degrees of outer segment development inside the photoreceptor rosettes, further confirming the maturation process and functional potential of the transplanted photoreceptor cells. Nuclear staining shows the presence of OPL-like spacing between the graft photoreceptors and host/graft INL. Graft INL (asterisk) is continuous from possibly merged host/graft INL (arrow).
F-G. Both graft and host rod bipolar cells appear to coexist in an INL-like structure after iPSC-retinal organoid sheet integration, and an OPL-like space is formed, where bipolar cells form synapses with the graft photoreceptor cells.