Fig. 4

Reduced tau phosphorylation by intravitreal injection of a GSK3β inhibitor protects RGCs from HFD-induced vision and synapse loss. (a) Western blotting for IRS-1, phosphorylated-Akt (S473), total Akt, phosphorylated-GSK3β (Ser9), total GSK3β in total retina lysate. Intensities were quantified and normalized against the level of GAPDH or total proteins (Akt or GSK3β) and expressed as percentage of protein abundance in the retina from HFD groups relative to their age-matched controls. Data are means ± SEM. n = 4 mice per group. ^*P < 0.05 and ^**P < 0.01 vs age-match RD controls. (b) A GSK3β specific inhibitor TWS119 or vehicle was injected intravitreally into the right eye (HFD-R-TWS119) or left eye (HFD-L-Veh), respectively, in mice fed with HFD for 20 weeks. Representative VEP waveforms and quantification of differences in peak amplitude (N1-P1) are shown. (c) Representative double immunostaining for phopho-tau (pS396- or pT205-Tau; green) with Tau-5 (Red), and for synaptophysin (green) with pT231-Tau (red). Scale bar, 100 μm. (d) Representative curvilineal profile of protein immunostaining intensity from GCL to OPL across the image shown in c. Data are means ± SEM. n = 5 eyes (b-d) per group. ^*P < 0.05 vs contralateral eye injected with vehicle