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SO Walker, J-Q Zheng, MA McDonald, MM Cruz, AA Sadun, JL Twiss, D-Y Wu; Differential MnSOD Expression in Retinal Ganglia: Suppressing Free Radical Toxicity Supports Retinal Ganglion Cell Survival After Optic Nerve Injury . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1991.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Much attention has been focused on the factors that influence retinal ganglion cell (RGC) survival. One mechanism of particular interest centers on an increase of free radical toxicity within the mitochondria as a cause for premature cell death. A key mitochondrial enzyme, manganese superoxide dismutase (MnSOD), serves as a main line of defense in the neuroprotection of RGCs against reactive oxygen species (ROS) after neuronal injury. Although the important role of MnSOD to destroy superoxide and its derivatives for neuronal survival is well known, the differential levels in MnSOD expression that exist within varying RGC survival states are not. Methods: Optic nerve of early postnatal (P3) CD1 mice was crushed. Five days later (P8), eyes were enucleated and processed to obtain neuroretina. Neuroretinae were dissociated and RGCs were selected using Thy-1 antibody-coated magnetic beads. Selected RGCs were subsequently used to obtain total RNA libraries that allowed for quantititative RT-PCR assessments of MnSOD levels between injured and non-injured RGC populations. Results: We found higher levels of ROS in RGCs after optic nerve crush. Concomitantly, we observed appproximately a 70% increase in mRNA levels of MnSOD in RGCs that survived injury compared to non-injured RGCs. Furthermore, suppression of MnSOD induced higher levels of cell death of RGCs in culture while reduction of ROS supported better RGC survival. Conclusion: The upregulation of MnSOD in surviving RGCs after optic nerve crush suggests that reduction of free radical toxicity within mitochondria is critical for RGC survival after injury. Given that mitochondrial health is required for cell survival, MnSOD expression may be used to assess the outcome of RGC survival after injury.
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