PGC-1 deficiency triggers gross morphological changes in the outer retina and RPE. PGC-1 deficiency triggers gross morphological changes in the outer retina.

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PGC-1 deficiency triggers gross morphological changes in the outer retina and RPE. PGC-1 deficiency triggers gross morphological changes in the outer retina and RPE. (A) Light micrographs from toluidine blue–stained semithin ocular sections from AAV-GFP and AAV-Cre–injected double floxed mice 4 mo postinjection showing severe disorganization of the RPE layer associated with prominent neuroretinal degeneration. Higher magnification of the RPE/choroid complex (corresponding to the dashed yellow boxes) shows degenerative lesion with swollen and sloughed RPE cells in the AAV-Cre–injected mice (arrows). Scale bars are 50 μm. (B–D) Transmission electron micrographs showing three representative examples of abnormal RPE in AAV-Cre–injected mice. Observed phenotypic changes vary from disorganized apical microvilli (arrowheads) with loss of basal infoldings (arrows) (B), massive accumulation of lipofuscin-containing granules (L) (C) to enlarged and dissociated cells filled with melanosomes (M) and undigested outer segments (OS) (D). Scale bars are 2 μm. (E) High magnification of the RPE basal side highlighting the prominent loss of basal infoldings (BI, double arrow), loss of fenestrations (*), thickening of the choriocapillaris endothelium, and severe mitochondria degeneration (arrows) marked by ruptured outer mitochondrial membranes and cristae remodeling (see insert). Scale bars are 500 nm. Mariana Aparecida Brunini Rosales et al. LSA 2019;2:e201800212 © 2019 Rosales et al.