Fig. 3

Massive intracellular accumulation of RPE-derived melanosomes in subretinal MPs of CD47^−/−-mice causes subretinal melanophage formation and their clinical appearance as hyperreflective foci. Representative sections (A–C and E–G) and 3D reconstructions (D and F) of serial block-face scanning electron microscopy (SBF-SEM) of 12-month-old Thbs1^−/−- (A–D), and Cd47^−/−-mice (E–H). Nuclei are indicated by asterixis, round orthogonally cut and spindle shaped longitudinally cut electron-dense melanosomes are indicated by magenta (in MPs) and blue (in RPE) arrows; melanolipofuscin by white arrows. The border of the subretinal MP (green color), and the surface of each melanosome (magenta) were marked on every SBF-SEM section containing the MPs (C and G) for the three-dimensional reconstruction of melanosome and melanolipofuscin particle distribution in the subretinal MPs (D and H and Additional file 1: Movie S1 and Additional file 2: Movie S2; other organelles were marked in white). Representative transmission bright light micrographs of RPE/retinal flatmounts, in which the RPE was kept adherent to the retina of 12-month-old mice of the indicated strains (I–K). Representative spectral-domain optic coherence tomography images of 12-month-old mice of the indicated strains (L–N). Blue arrows indicate the RPE hyperreflective line and red arrows indicate retinal hyperreflective lesions. Thbs1 thrombospondin 1 gene, OS outer segments of photoreceptors, RPE retinal pigment epithelium. Scale bar = 2 µm