Figure 8.

Modified M³⁶³R NS administration in NS^−/− mice protects against retinal deficits in chronic glaucoma

(A and B) pSTR traces in WT and NS^−/− mice under control conditions (A) and (B) pSTR traces in WT and NS^−/−-, NS^−/− + WT-NS-, and NS^−/− + M³⁶³R-NS-administered mice under experimental glaucoma conditions. (C) Quantification of pSTR amplitudes demonstrated significantly lower pSTR amplitudes in NS^−/− compared with WT mice at 3 months of age (p < 0.0001, n = 10 animals/group). Induction of experimental glaucoma reduced pSTR amplitudes in WT and NS^−/− mouse retinas. NS administration (10 μmol/L; volume, 2 μL; once weekly for 8 weeks) demonstrated enhanced pSTR amplitudes; however, protection with M³⁶³R-NS was much higher compared with WT NS treatment in experimental glaucoma (p < 0.031, n = 10 animals/group). (D) H&E analysis of retinal sections from WT and NS^−/− mice in control and glaucoma along with WT and M³⁶³R-NS-treated groups under glaucoma conditions. Arrows indicate the GCL. (E) There was a significant decrease in GCL density in NS^−/− compared with WT mouse retinas under the control condition (p < 0.0001). M³⁶³R-NS administration in experimental glaucoma significantly protected GCL density compared with the WT NS-administered group (p < 0.007, n = 4 animals, 3 sections/animal). (F and G) TUNEL apoptosis staining and its quantification revealed positive cells in NS^−/− mouse retinas, which was significantly enhanced in glaucoma (p < 0.0001). WT NS (p < 0.001 control, p < 0.0001 glaucoma) and M³⁶³R-NS (p < 0.008 control, p < 0.002 glaucoma) administration under control and glaucoma conditions led to a significant reduction in TUNEL⁺ staining in the GCL. TUNEL⁺ cells (red) are predominantly in the GCL layer. Reduced TUNEL⁺ cells were evident in animals subjected to M³⁶³R-NS administration compared with the WT NS-administered group. DAPI, blue. n = 3 animals/group. Scale bars, 50 μm. Graphs show means ± SEM, and p values were obtained using Student’s t test.