Cross-species molecular mapping of the photoreceptor sensory cilium and periciliary complexes identifies conserved and species-specific architectural features

Photoreceptor sensory cilia (PSCs) support outer segment formation and are associated with specialized periciliary complexes, yet their cross-species and subtype-dependent organization remains incompletely defined. Here, we used ultrastructure expansion microscopy to compare PSC architecture and associated periciliary complexes across canine, non-human primate (NHP), and human retinas. Across all three species, rods and cones shared a conserved subtype-dependent organization, with cones displaying shorter connecting cilia (CCs), longer daughter centrioles (DCs), and enlarged bulge regions relative to rods. However, the scale and elaboration of these structures differed substantially between species, with primate PSCs showing shorter CCs, more pronounced widening of the apical region, and elongated cone DCs. Periciliary complexes showed even greater diversification. Canine rods exhibited a unilateral periciliary membrane and lacked calyceal process, whereas primate rods and cones of all three species showed a circumferential periciliary membrane and robust calyceal process. Human photoreceptors were broadly NHP-like but revealed variable accessory inner segment-like structures. Together, these findings provide a comparative nanoscale framework for photoreceptor ciliary organization in large mammals and show that conserved PSC principles coexist with pronounced species- and subtype-specific specialization.