Research Paper Volume 12, Issue 13 pp 13437—13462

Loss of β-catenin via activated GSK3β causes diabetic retinal neurodegeneration by instigating a vicious cycle of oxidative stress-driven mitochondrial impairment


Figure 2. Oxidative stress causes mitochondrial defect and synaptic neurodegeneration in diabetic retinae. (A) Contents of 4-HNE in retinae. (B) Activities of antioxidant enzymes. (C) Expression of genes encoding ROS scavengers was determined by quantitative RT-PCR in retinae. The mRNA level of each gene was normalized to the internal GAPDH control and expressed as fold changes of mRNA abundance in the retina from HFD groups relative to their age-matched RD controls. (DH) 1 μl of NAC (500 nM) was injected intravitreally into the right eye of HFD-induced diabetic mice (HFD-R/+NAC), while PBS was injected into the contralateral left eye as a control (HFD-L/-NAC). (D) Representative waveforms of VEP and quantification of differences in peak amplitude (N1-P1). (E) Contents of retinal 4-HNE. (F) Representative images of retinal TEM with mitochondria in IPL (arrows). Areas boxed in are shown at higher magnification in the lower panels. Scale bar, 0.5 μm. (G) Representative SEM of retinal sections. Areas boxed are shown at higher magnification. Scale bar, 10 μm. (H) Representative synaptophysin (green; scale bar, 100 μm) immunostaining in retinae. Areas boxed in are shown at higher magnification in the lower panels. Data are means ± SEM. n = 4 mice (AC) or n = 4 eyes (DH) per group. **P < 0.01 vs age-match RD controls; *P < 0.05 and **P < 0.01 vs contralateral eye injected with PBS. See also Supplementary Figures 2B and 3B.