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Traditional strategies to mitigate immune rejection involve ablating major histocompatibility complex (MHC) molecules on hESC\u2010RPE. An alternative approach is immune checkpoint overexpression, avoiding natural killer (NK) cell\u2010mediated destruction due to MHC\u2010I deficiency. Our study highlights the benefits of PD\u2010L1 overexpression without requiring MHC gene deletion, which preserved the immunosuppressive functions of hESC\u2010RPE on NK cells. In\u00a0Vivo experiments in retinal degeneration models showed that PD\u2010L1\u2010expressing hESC\u2010RPE grafts exhibited significantly higher survival, reduced apoptosis and enhanced visual protection. Single\u2010cell transcriptomics revealed reduced immune activation and oxidative stress in PD\u2010L1\u2010overexpressing grafts. PD\u2010L1's protective role was further evidenced by improved light transduction in host photoreceptors. 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