Fig 2: Scotopic retinal function of rod?Vhl, rod?Vhl;Hif1a, rod?Vhl;Hif2a, and rod?Vhl;Hif1a;Hif2a mice at 6 months of age. a Scotopic ERG traces were recorded after light stimuli of increasing light intensities. Shown are representative traces. Cre-negative Vhlflox/flox mice served as controls. b Scotopic a-wave and b-wave amplitudes plotted as a function of stimulus intensity. Control mice were Cre-negative littermates of the respective strains. Shown are averages ± SD. N = 6 eyes (3 mice), except for controls of rod?Vhl;Hif2a (N = 5) and of rod?Vhl;Hif2a (N = 7), and for rod?Vhl;Hif1a;Hif2a (N = 4). *P < 0.05. Two-way ANOVA with Sidak’s multiple comparison test

Fig 3: Consequences of chronically activated HIF transcription factors in rods. a Retinal morphology was tested at 11 weeks, 4 months, 6 months, and 1 year of age as indicated. Cre-negative Vhlflox/flox mice served as controls. RPE retinal pigment epithelium, POS photoreceptor outer segments, PIS photoreceptor inner segments, ONL outer nuclear layer, INL inner nuclear layer. Scale bar: 50 µm. N = 3. b ONL thicknesses in indicated strains were determined at 11 weeks and 6 months of age and are presented as spidergrams. Shown are means ± SD of N = 3, except for Vhlflox/flox mice at 6 months (N = 2). c Expression of Gnat1 and Gnat2 in rod?Vhl (V), rod?Vhl;Hif1a (VH1), rod?Vhl;Hif2a (VH2), and rod?Vhl;Hif1a;Hif2a (VH1H2) mice at 11 weeks and 6 months of age. Expression levels were calculated relative to their respective Cre-negative controls (set to 1; dotted line). Shown are means ± SD of N = 3-4. *P < 0.05; **P < 0.01. Individual comparisons between Cre-positive and Cre-negative mice of each genotype and time point were done using Student’s t-test