Figure 4.

NS overexpression protects inner retinal function and structure in chronic glaucoma

(A) Sustained IOP elevation in WT and NS^{+/+ Tg} animal eyes for 8 weeks following microbead injections. (B) pSTR responses in normal and chronic glaucoma models of WT (blue and red) and NS^{+/+ Tg} (orange and black) retinas. (C) No change in pSTR amplitude was observed in WT and NS^{+/+ Tg} mice under normal conditions. Significant differences were observed among the pSTR amplitudes of WT mice exposed to chronically elevated IOP (p < 0.0001), which are more susceptible to glaucomatous damage compared with their NS^{+/+ Tg} counterparts (p < 0.0001, n = 10 animals/group), which represents remarkable protection in inner retinal function under similar conditions. (D) Histological analysis of paraffin-embedded retinal sections from WT and NS^{+/+ Tg} stained by H&E. Arrows indicate GCL. Scale bars, 50 μm). (E) There was a significant decrease in GCL cells in WT mice under chronic elevation of IOP (p < 0.0001; n = 4 animals, 3 sections/animal) compared with NS^{+/+ Tg} mice (p < 0.0001; n = 6 animals in each group). (F) Cross-sections of WT and NS^{+/+ Tg} ON with or without high IOP counterstained with TB. Scale bars, 20 μm. (G) Quantification (TB) indicating a significant decline in axon density in WT compared with NS^+/+Tg mice under high IOP (n = 4 animals, 3 sections/animal; p < 0.0001 and p < 0.0001). (H) Increased TUNEL⁺ staining (red) was observed in WT retinal sections exposed to high IOP compared with NS^{+/+ Tg} mouse retinas under experimental glaucoma in the GCL (white arrows). Shown are DAPI-stained cell nuclei (blue). Scale bars, 50 μm), (I) Quantification of TUNEL⁺ cells showing significantly increased numbers in WT retinas exposed to high IOP compared with NS^{+/+ Tg} retinas (n = 3 animals in each group, p < 0.0003). Graphs show means ± SEM, and p values were obtained using Student’s t test.