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Kyle I. Swanson, Christopher R. Schlieve, Christopher J. Lieven, Leonard A. Levin; Neuroprotective Effect of Sulfhydryl Reduction in a Rat Optic Nerve Crush Model. Invest. Ophthalmol. Vis. Sci. 2005;46(10):3737-3741. doi: 10.1167/iovs.05-0155.
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purpose. The signaling of retinal ganglion cell (RGC) death after axotomy is partly dependent on the generation of reactive oxygen species. Shifting the RGC redox state toward reduction is protective in a dissociated mixed retinal culture model of axotomy. The hypothesis for the current study was that tris(2-carboxyethyl)phosphine (TCEP), a sulfhydryl reductant, would protect RGCs in a rat optic nerve crush model of axotomy.
methods. RGCs of postnatal day 4 to 5 Long-Evans rats were retrogradely labeled with the fluorescent tracer DiI. At approximately 8 weeks of age, the left optic nerve of each rat was crushed with forceps and, immediately after, 4 μL of TCEP (or vehicle alone) was injected into the vitreous at the pars plana to a final concentration of 6 or 60 μM. The right eye served as the control. Eight or 14 days after the crush, the animals were killed, retinal wholemounts prepared, and DiI-labeled RGCs counted. Bandeiraea simplicifolia lectin (BSL-1) was used to identify microglia.
results. The mean number of surviving RGCs at 8 days in eyes treated with 60 μM TCEP was significantly greater than in the vehicle group (1250 ± 156 vs. 669 ± 109 cells/mm2; P = 0.0082). Similar results were recorded at 14 days. Labeling was not a result of microglia phagocytosing dying RGCs. No toxic effect on RGC survival was observed with TCEP injection alone.
conclusions. The sulfhydryl-reducing agent TCEP is neuroprotective of RGCs in an optic nerve crush model. Sulfhydryl oxidative modification may be a final common pathway for the signaling of RGC death by reactive oxygen species after axotomy.
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