Novel Compound SA-21 with Antioxidant Capability - The Prospect for Neuroprotection in Glaucoma.

Purpose: Current treatments for glaucoma do not fully address neurodegeneration of retinal ganglion cells (RGCs). Our objective was to determine if compound SA-21, a hybrid superoxide dismutase and glutathione mimetic, could inhibit death of trabecular meshwork cells (NTM5), RGCs and rescue the functional decline of RGCs in an optic nerve crush (ONC) model. Methods: The structure of SA-21 was confirmed by magnetic resonance (NMR) spectroscopy and mass spectrometry. Reactive oxygen species (ROS) release was performed using pyrogallol assay. NTM5 cells were oxidatively stressed with TBHP (5.5mM) or vehicle in the presence of SA-21 (1mM, 100µM, 10µM, 1µM) for 24h. Cell survival was assessed by MTT assay. C57BL6 male mice (12-weeks old, n=4-5) were anesthetized, underwent ONC surgery, and at day 0 and 3 were intravitreally injected with 1% SA-21 (2µl) or vehicle. On day 7, pattern electroretinogram (PERG) was performed, animals were euthanized, and the number of surviving RBPMS-positive RGCs were counted. Results: SA-21 (1mM) treatment significantly decreased ROS production (~50%) measured by pyrogallol assay and increased NTM5 cell viability (~20%, p< 0.0094) following TBHP treatment compared to cells treated with the vehicle. ONC produced a 48% loss of RGCs, which was decreased in SA-21 treated mice (by ~10%) and demonstrated a trend in increase in PERG amplitude. Conclusions: SA-21 compound has antioxidant capability and protects NTM5 cells from oxidative stress. Intravitreally injected SA-21 at the selected dose in mice demonstrated trend in neuroprotection but further investigation is required.