TNF-α mediates the effect of increased IOP on oligodendrocytes. A–F, Representative merged photomicrographs showing APC⁺ oligodendrocytes (green) and DAPI nuclear staining (blue) in longitudinal sections through the optic nerve with or without TNF-α treatment. Shown are control (A) and 1 d (B), 4 d (C), and 14 d (D) after TNF-α injection. E, F, APC⁺ oligodendrocytes in the optic nerve after direct contact with a Spongel soaked in 1 ng/ml TNF-α solution (E) or PBS (F) after 14 d. Scale bar, 50 μm. G, Time course of oligodendrocyte degeneration after intravitreal administration of PBS (diamond) or TNF-α (square). Also shown are survival data 14 d after direct administration of PBS (triangle) or TNF-α (circle) to the optic nerve. **p < 0.01, ***p < 0.001 compared with PBS-treated controls (n = 8 per time point). H, APC⁺ oligodendrocytes in optic nerves treated with anti-TNF-α blocking antibody or normal goat serum (NGS) 14 d after inducing OH. Scale bar, 50 μm. I, Quantitation of OH-induced oligodendrocyte degeneration after 14 d. ***p < 0.001 compared with normal controls (n = 8). J, Quantitation of OH-induced oligodendrocyte degeneration 14 d after inducing OH in wild-type or TNF-α^−/− mice. ***p < 0.001 compared with normal control (n = 8).