Fig. 3

PrPSc accumulates first in cone photoreceptor inner segments. a At 67 dpi, rare small punctate PrPSc deposits (arrow) are present on cone photoreceptors marked with Cone Arrestin (green). Magenta in outer segment is autofluorescence of rhodopsin. b Cone opsin (white) marks cone outer segments with PrPSc (magenta) deposits associated mainly with cone inner segments (yellow arrow) at 104 dpi. The transition from faint to intense cone opsin staining marks the boundary between cone IS and cone OS (blue arrow). c Another cone-specific outer segment protein GNAT2 (green) shows obvious connection with PrPSc (magenta) staining cone inner segments at 104 dpi (arrows). d At 104 dpi, rod-specific marker, GNAT1 (green) stains rod inner and outer segments, but spares cones (arrowheads). PrPSc (magenta) accumulations are present in the dark GNAT1-free areas (arrows). e A separate experiment done with 22L scrapie strain shows same association of PrPSc with cone inner segments at 123 dpi, suggesting cone specificity is not strain-specific. Scale bar = 5 µm. a, b, d are confocal z-stacks, c, e are widefield images