FIG. 1.

Activation of ER stress and upregulation of ATF4 colocalized with VEGF in retinal Müller cells in diabetic mice. Diabetes (DM) was induced in 8-week-old C57 mice by five consecutive STZ injections (50 mg/kg/day). ER stress markers in the retina were examined at 4 weeks after STZ injection. A: Immunohistochemistry showing increased p–eIF2-α/ATF4/CHOP (green) partially colocalized with Müller cell marker GS (red) in diabetic retinas. Scale bar = 50 μm. B: Western blot analysis showing increased phosphorylation of IRE1-α and eIF2-α and elevated ATF4 and VEGF expression in diabetic retina. Bar graphs represent quantification results using densitometry (mean ± SD, n = 4). *P < 0.05, **P < 0.01 vs. control. C: Double staining of ATF4 (green) and VEGF (red) in retinal sections from diabetic and control mice. Scale bar = 50 μm. (A high-quality digital representation of this figure is available in the online issue.)