Fig. 5

Early PrPSc accumulation and damage in the inner segment. a Cartoon of cone photoreceptor shows key structures related to PrPSc deposition. cc connecting cilium, bb basal body, r rootlet, m mitochondria, cp cone pedicle, rs ribbon synapse. b Anti-centrin3 antibody (green) marks the connecting cilium and basal body (small green dots) of all photoreceptors. PrPSc (magenta) accumulation at entrance to connecting cilium (arrow), magnified in inset. c Serial 0.5 µm confocal sections (c1–6) showing relative localization of PrPSc, cilium and basal body. d Cone arrestin (green) staining of uninfected cone photoreceptor. Arrow indicates likely position of connecting cilium. e 118 dpi shows retina stained for cone arrestin (green) and PrP (magenta). Asterisks mark cones missing outer segments, yellow arrows point to position of connecting cilia and associated PrPSc (magenta) deposit, and arrowheads show dystrophic outer segments. f, g Confocal analysis showing xy and yz planes of swollen cones from e confirm the presence of PrPSc at the location of the connecting cilium (arrow) between the IS and OS. h In an uninfected retina, anti-rootletin (green) antibody stains the rootlets of photoreceptors. i, j At later days post infection, PrPSc (magenta) is increased, rootlets are fewer in number and misshapen. Scale bars: b, e = 5 µm; c = 1 µm; d = 2 µm; f, g = 2 µm; h = 10 µm. b, d, e Maximum intensity projections (MIP) of confocal z-stacks h, i, j are widefield images