Allogenic Transplantation of RPE Strips Lacking MHC Class II Can Avoid Rejection in Nonhuman Primate Eyes

We previously reported that suspensions of CIITA-/- monkey induced pluripotent stem cell-derived retinal pigment epithelium (moiPSC-RPE) that lacks expression of major histocompatibility complex (MHC) class Ⅱ avoided rejection without systemic immunosuppression. RPE strips represent a novel graft formulation for RPE impairment diseases that may enable mass engraftment but potentially increase rejection risk. This study evaluated host immune responses to allogeneic CIITA+/+ and CIITA-/- moiPSC-RPE strips in MHC-mismatched transplantation in monkey eyes with RPE damage, without systemic immunosuppression.

RPE strips were generated from CIITA+/+ and CIITA-/- moiPSC-RPE. Following RPE ablation using a microsecond pulse laser, two RPE strips were transplanted into each eye at 1- to 3-week intervals. One monkey received CIITA+/+ moiPSC-RPE strips, while another received CIITA-/- moiPSC-RPE strips. Graft status was monitored through routine ophthalmic examinations, and immunohistologic evaluation was conducted after 5 months.

Fluorescein angiography revealed evident leakage in eyes with CIITA+/+ RPE strips beginning 1 to 2 months posttransplantation, with optical coherence tomography showing bulging at the graft site, indicating immune cell accumulation. Immunostaining confirmed the presence of immune cells (CD4, CD8, Iba1, IFN-γ, MHC class II, and CD20) at CIITA+/+ RPE strip grafts. In contrast, CIITA-/- RPE strip transplants showed no signs of rejection in either eye over 5 months and minimal immune cell presence at the graft site.

Allogeneic transplantation of CIITA-/- RPE strips may reduce rejection risk in RPE-ablated disease model eyes, suggesting potential clinical benefits of MHC class II-deficient RPE grafts, particularly for diseases with inflammatory pathology.