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Abstract
PURPOSE: To determine whether the lipid peroxidation inhibitor tirilazad mesylate can block the death of retinal ganglion cells induced by the inhibition of oxidative phosphorylation and glycolysis. METHODS: Rat retinal ganglion cells were labeled retrogradely with the fluorescent tracer DiI, and mixed cultures were prepared. Cell death was induced with chemical hypoxia, hypoglycemia, or glycolysis inhibition, and the effect on cell survival of tirilazad mesylate was assessed. RESULTS: Tirilazad mesylate enhanced relative ganglion cell survival after plating, with detectable effects at 200 nM and a maximal increase above diluent control of 148% +/- 2% at 20 microM. Relative survival at 24 hours in the presence of the complex IV inhibitor sodium cyanide (3 mM) was significantly greater when it was co-incubated with tirilazad mesylate than with diluent control (91.8% +/- 4.6% versus 39.3% +/- 7.1%; P = 0.008). Enhanced relative survival with tirilazad mesylate also was seen in cultures containing reduced glucose media. CONCLUSIONS: The lipid peroxidation blocker tirilazad mesylate inhibits retinal ganglion cell death in vitro. Because irreversible loss of retinal ganglion cells is the final common pathway in a variety of optic neuropathies, this or similar agents may be useful in animal models of optic neuropathies.