Figure 3
SRTAW04 treatment prevents neuronal loss in MHV-A59 infected mice. (a) MHV-A59 (n = 28) infection significantly decreases RGC numbers compared to non-infected control mice (n = 18) (***p < 0.001). SRTAW04 treatment (100 mg/kg/day) for 30 days (n = 16) results in significant (@@p < 0.01) attenuation of RGC loss. (b) C57BL/6 mice were inoculated with recombinant strain of MHV, RSA59 and the treatment group was administered SRTAW04 (100 mg/kg/day) for 30 days with and without SIRT1 inhibitor EX527 (10 mg/kg/day i.p.). After 30 days the RGCs were labeled by Brn3a staining and counted. RSA59 (n = 12) induced a significant decrease in RGCs (***p < 0.001) compared to control (n = 8) and MHV2 infected (n = 6) mice. Treatment with SRTAW04 (n = 10) significantly (@@@p < 0.001) attenuated RGC loss. The SRTAW04 treatment group receiving EX527 (n = 10) showed a significant decrease (*p < 0.05) in RGC numbers compared to the group that only received SRTAW04 demonstrating that the RGC protective effect of SRTAW04 is dependent on SIRT1. Brn3a labeled RGCs from a representative retinal field in (c) control, (d) RSMHV2 infected, (e) RSA59 infected, (f) RSA59 infected, with SRTAW04 treatment and (g) RSA59 infected, with SRTAW04 + EX527 treatment. Fewer RGCs are seen in a corresponding area of retina in an MHV-A59 infected mouse. Retina from an MHV-A59 infected mouse treated with SRTAW04 (100 mg/kg/day) for 30 days shows numerous RGCs similar to the non-infected control whereas MHV-A59 infected mouse treated with SRTAW04+ EX527 for 30 days shows fewer RGCs. Scale bars 10 μm for c-g.