Fig 1: Abnormal RPE histology in MELAS patient eyes.(A and B) Ezrin staining in control RPE indicates proper polarization of mature epithelium. Panel B shows a negative control section stained with secondary antibody against mouse IgG but without primary antibody against EZR. (C and D) Dimmer and less polarized ezrin signal is observed in MELAS patient RPE. Scale bar: 25 µm (A–D). (E) A mass of pigmented cells at the layer of the RPE in a MELAS patient eye. (F) Pigmented cells display autofluorescence in the green and red channel (yellow overlay shown), indicating the presence of lipofuscin normally found in RPE cells. (G) Ezrin staining of the RPE layer is lost at the border of the pigmented lesion (Alexa Fluor 647 fluorescence pseudocolored magenta). Scale bar: 50 µm (E–G). (H and I) Compared with healthy donor RPE, MELAS RPE appears generally thinned and hypopigmented. Hypertrophied cells are observed. (J) Migration of pigmented cells into the neural retina is observed in a MELAS eye (arrow), indicating dedifferentiation of RPE. (K) Early-stage outer retinal tubulation over a patch of thinned RPE is observed in a MELAS eye. Scale bar: 50 µm (E–G). RPE, retinal pigment epithelium; CC, choriocapillaris; INL, inner nuclearlayer; OPL, outer plexiform layer; ONL, outer nuclear layer.