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

Area of Science:

• Ophthalmology
• Immunology
• Regenerative Medicine

Background:

• Retinal pigment epithelium (RPE) impairment diseases pose significant challenges for treatment.
• Novel graft formulations like RPE strips aim for mass engraftment but risk increased immune rejection.
• Previous work showed CIITA-/- monkey induced pluripotent stem cell-derived RPE (moiPSC-RPE) avoids rejection without systemic immunosuppression.

Purpose of the Study:

• To evaluate host immune responses to allogeneic CIITA+/+ and CIITA-/- moiPSC-RPE strips.
• To assess the efficacy of MHC class II-deficient RPE strips in a monkey eye transplantation model with RPE damage.
• To determine if MHC class II deficiency mitigates rejection without systemic immunosuppression.

Main Methods:

• RPE strips were generated from CIITA+/+ and CIITA-/- moiPSC-RPE.
• RPE was ablated using a laser, followed by transplantation of RPE strips into monkey eyes.
• Graft status and immune responses were monitored via ophthalmic exams and immunohistologic evaluation for 5 months.

Main Results:

• Eyes receiving CIITA+/+ RPE strips showed signs of immune rejection, including leakage and immune cell accumulation.
• Immunostaining confirmed significant presence of immune cells and MHC class II in CIITA+/+ grafts.
• CIITA-/- RPE strip transplants exhibited no rejection and minimal immune cell infiltration over the 5-month study period.

Conclusions:

• Allogeneic transplantation of MHC class II-deficient CIITA-/- RPE strips may reduce rejection risk in RPE-ablated eyes.
• These findings suggest potential clinical benefits of MHC class II-deficient RPE grafts for RPE diseases.
• This strategy could be particularly advantageous for diseases with inflammatory components.