Fig. 4

Proteomic landscape of \(rod^{\varDelta \ Vhl}\) PS and ONL. a Photoreceptor segments (PS) and the outer nuclear layer (ONL) were isolated from six \(rod^{\varDelta \ Vhl}\) and six ctrl mice and their proteomic landscape analysed by LC-MS/MS. b Principal component analyses of the PS and ONL proteomes from \(rod^{\varDelta \ Vhl}\) and ctrl mice. c Heatmap of the top 25 up- and downregulated proteins in the ONL compared to the PS samples of all 12 mice. Proteins belonging to the phototransduction cascade, cilium, mitochondria or nucleus are indicated. d,e Volcano plots showing differentially up- (red) and downregulated (blue) proteins in the ONL (d) and PS (e) of \(rod^{\varDelta \ Vhl}\) mice compared to ctrl. Total number of differentially regulated proteins as indicated. Threshhold: p \(\le\) 0.05. f Representative immunofluorescence labeling for GLUT3 in \(rod^{\varDelta \ Vhl}\) and ctrl retina. Scale bar, 50 \(\upmu\)m. N = 3 mice per genotype. g,h Gene set enrichment analyses using the MSigDB hallmark dataset. Enrichment of proteins of the hallmark HYPOXIA (g) and OXPHOS (h) in the ONL and PS of \(rod^{\varDelta \ Vhl}\) and ctrl mice as indicated. The top of each panel shows the running enrichment score (green) for the gene set. The lower part of each panel shows the position of identified members of the gene set (black lines: hits, red to blue gradient: strength of enrichment in \(rod^{\varDelta \ Vhl}\) and control (ctrl) mice) in the ranked list of proteins. For statistical analysis on proteomics data see Methods. NES: normalized enrichment score. PS: photoreceptor segments. ONL: outer nuclear layer. INL: inner nuclear layer. IPL: inner plexiform layer. GCL: ganglion cell layer