Fig. 5

Dysregulation of OXPHOS in rods with chronically active HIFs. a,b Representative in situ enzymatic staining for COX (a) and SDH (b) activity in \(rod^{\varDelta \ Vhl}\), \(rod^{\varDelta \ Vhl;Hif1\alpha }\), \(rod^{\varDelta \ Vhl;Hif2\alpha }\) and ctrl mice at time points as indicated. Shown are all retinal layers (top panels), a magnification of the photoreceptor segments (PS; boxed area, middle panels), and pixel intensity (PI) profiles through the PS (bottom panels). Black arrows indicate regions with reduced COX or SDH activity. N = 3 mice per genotype. c Representative immunofluorescence labeling for COX4i1 in the PS region of \(rod^{\varDelta \ Vhl}\), \(rod^{\varDelta \ Vhl;Hif1\alpha }\), \(rod^{\varDelta \ Vhl;Hif2\alpha }\) and ctrl mice at 2.5 months of age (top panels). PI profiles through the PS (bottom panels). White arrows indicate regions with reduced COX4i1 labeling. N = 3 mice per genotype. d Representative immunofluorescence labeling for Cre (green) and COX4i1 (red) in the ONL and PS regions of \(rod^{\varDelta \ Vhl}\) mice at 2.5 months of age. White arrows indicate regions with reduced COX4i1 labeling in the IS of Cre-positive cells. N = 3 mice. e Significantly downregulated OXPHOS complex subunits and assembly factors and upregulated complex V inhibitory factor ATPIF1 in the PS of \(rod^{\varDelta \ Vhl}\) mice at 2.5 months of age. N = 6  mice per genotype. For statistical analysis on proteomics data see Methods. ONL: outer nuclear layer. OPL: outer plexiform layer. INL: inner nuclear layer. IPL: inner plexiform layer. GCL: ganglion cell layer. Scale bars, 50 \(\upmu\)m