GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE304nnn/GSE304621/primaryOK200TranscriptomicsMacaca mulattaExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE304621GEOGSEfalseSingle-cell and spatial transcriptomic analyses of gene therapy-associated retinal inflammation in non-human primates [scRNA-seq]Adeno-associated viral (AAV) vectors are rapidly advancing as gene therapies for inherited and common retinal disorders, but gene therapy-associated uveitis (GTAU) limits their broader application. To investigate the primate ocular immune response, we administered subretinal AAV gene therapy to two non-human primates (NHPs): NHP1 received AAV2-CAG-hRPE65 (voretigene neparvovec) bilaterally at clinical dose; NHP2 received AAV8-GRK1-hRPGRco alongside an analogous mScarlet reporter vector in separate blebs. Longitudinal assessments over three months included multimodal imaging, electroretinography and cytokine profiling, followed by immunohistological, single-cell and spatial transcriptomic analyses of retinal punches. Both therapies were well-tolerated, with preserved retinal structure and function. Single-cell RNA-sequencing revealed that the AAV8 vector transduced 80% of cones/rods in treated areas, while AAV2 targeted 30% of retinal pigment epithelium (RPE)/rods. Transgene expression did not correlate with apoptotic markers. Persistent immune infiltration (dominated by myeloid and T cells) suggested a type 1 cell-mediated response. Adjunctive intravitreal anti-TNFα (adalimumab) did not appear to mitigate this anti-viral response. Spatial analysis highlighted microglia migration to the subretinal space, consistent with upregulated cytokines (MCP-1/CCL2, IP-10/CXCL10, IL-8/CXCL8, IL-6), which implicate monocytic phagocytes in driving local inflammation. These findings elucidate the mechanism of GTAU and identify potential therapeutic targets to prevent immune-mediated complications in retinal gene therapy.2026/03/30GSE304621GSM9154224GSM9154225GSM9154216GSM9154220GSM9154221GSM9154222GSM9154223GSM9154217GSM9154218GSM915421934625304621Macaca mulatta