Abstract
Abstract: :
Purpose: We previously demonstrated that shifting the retinal ganglion cell redox state towards mild reduction is protective in a dissociated mixed retinal culture model of axotomy. We wished to determine whether TCEP, a sulfhydryl reductant, protects retinal ganglion cells following optic nerve crush in vivo. Methods: Retinal ganglion cells of postnatal day 2–4 Long Evans rats were retrogradely labeled with 1,1'–dioctadecyl–3,3,3',3'–tetramethylindocarbocyanine perchlorate (DiI). At approximately 8 weeks of age the left optic nerve of each rat was crushed with fine forceps approximately 4 mm behind the globe. At the same time 4 µl TCEP dissolved in saline (or saline alone) was injected into the vitreous at the pars plana to a final concentration of 100 µM. The right eye served as a control. Eight days after the crush, animals were sacrificed and retinal whole mounts prepared. DiI–labeled ganglion cells near the optic disc were then counted by an observer masked to treatment or presence of crush. Results:The mean number of surviving retinal ganglion cells in the TCEP group was 1736±96.2 cells/mm2, significantly greater than the saline group which had 636±82.8 cells/mm2 (p<0.001). Studies with a novel TCEP derivative at sub–micromolar concentrations in cell culture experiments also showed positive effects on survival without neurotrophic factors at 72 hours (91±13 living cells/well vs. 6±4; p=0.025). Conclusions: TCEP has a neuroprotective effect on retinal ganglion cells in an optic nerve crush model.
Keywords: neuroprotection • retina • ganglion cells