Previous work has shown that potassium bisperoxo (1,10-phenanthroline) oxovanadate, BpV(Phen), is a potent protein phosphotyrosine phosphatase (PTPase) inhibitor that preferentially blocks the activity of Phosphatase Tensin Homologue Deleted on Chromosome Ten (PTEN). Currently, it remains unknown how pharmacological inhibition of PTEN by bpV(phen) impacts the survival of mammalian RGCs. Thus, the current study investigated the effect of bpV(phen) on RGC survival in vitro and in vivo and the mechanism mediating this outcome following bpV(phen) administration. Collectively, this study revealed that bpV(phen) promoted survival of injured retinal ganglion cells from mature animals (postnatal day 21 (P21) and adult mice) after injury in vitro and in vivo. Interestingly, data also showed bpV(phen) to have an antagonistic effect on healthy RGCs and promote apoptosis. Lastly, preventing Smad3 from being phosphorylated in the transforming growth factor β (TGF-β) pathway did not augment the survival in bpV(phen)-treated RGCs.