Abstract
Purpose:
Recently, we reported that Vitamin E-TPGS could exacerbate the toxicity of dimethylsulfoxide (DMSO) in RGC-5 cells, through inhibition of the multidrug efflux channel P-glycoprotein (P-gp) (Butt et al, 2014. Invest Ophthalmol Vis Sci;55: E-Abstract 1709). The present study sought to determine whether a similar trend occurred in primary retinal cell cultures and whether CoQ10, which is a potential neuroprotective agent, could alter these changes.
Methods:
Cell viability experiments were performed in the presence of DMSO and varying concentrations of vitamin E-TPGS and vitamin E-TPGS/CoQ10 in mixed retinal cultures and primary murine Retinal Ganglion Cells (RGCs). Cell survival was measured after 24h exposure to cytotoxic insults including DMSO and vitamin E-TPGS with or without CoQ10 using the AlamarBlue viability assay.
Results:
In agreement with previous results using immortalized cells, vitamin E-TPGS treatment of mixed retinal cultures was found to significantly exacerbate the toxicity of DMSO insult in a dose dependent manner (Pearson’s r=-0.9331, p=0.007). In contrast, CoQ10 treatment with Vitamin E-TPGS was found to abolish this effect (Pearson’s r=0.052, p=0.664). Similar results were obtained using primary RGC cultures.
Conclusions:
Vitamin E-TPGS mediated P-gp inhibition was previously reported to increase immortalized retinal cell susceptibility to DMSO insult. The present study provides evidence to suggest a similar phenomenon occurs in primary retinal cultures. However, the presence of the antioxidant CoQ10 abolishes this effect, underlining its neuroprotective effects through different intracellular mechanisms.