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Kenya Yuki, Seiji Miyake, Tetsu Yoshida, Kazuo Tsubota, Yoko Ozawa; Protective Role of Superoxide Dismutase 1 in the retina against NMDA-induced neurotoxicity. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4764.
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Superoxide dismutase 1 (SOD1) is an enzyme that metabolizes superoxide anion, one of reactive oxygen species. It binds the metal cofactor, copper and zinc, and acts in the cytosol. N-methly-D-aspartic acid (NMDA) is an amino acid which mimics the action of glutamate and is a well-known excitotoxin. Its toxicity is reported to be associated with ischemia-reperfusion injury, Alzheimer disease, and glaucoma. In this study, we analyzed the role of SOD1 on NMDA induced-neurotoxicity in the retina.
Eight-week old SOD-1 knock-out (SOD1KO) mice (C57BL/6J background) and the control wild type (SOD1WT) mice were prepared, and NMDA was administered as follows. After anesthetized with diethyl ether, 2 μl of either 10mM NMDA or phosphate-buffered saline (PBS) was injected intravitreally using a Hamilton syringe with a 32-G needle. First, the levels of SOD1 in the retina in SOD1WT mice were measured by immunoblot analysis at 24 hours after the injection (n=8,9). Then, the apoptotic cells were counted using TdT-dUTP terminal nick-end labeling (TUNEL) in the retinal cryosections cut through the vertical meridian including the optic nerve head, and compared between SOD1KO and SOD1WT mice (n=5).
The level of SOD1 in the retina significantly increased at 24 hours after 10 mM NMDA administration compared to PBS administration in the SOD1WT mice (SOD1WT-PBS 1.0±0.1, SOD1WT-10mM NMDA 1.8±0.4, p<0.01 t-test). After injection of 10 mM NMDA, the number of TUNEL positive cells in the inner nuclear layer (INL) of SOD1KO mice was significantly larger than in the INL of SOD1WT mice (SOD1WT-PBS; 0.0±0.0 cells, SOD1WT-10mMNMDA; 163.8±8.4 cells, SOD1KO-PBS; 0.0±0.0 cells, SOD1KO-10mMNMDA; 208.0±11.0 cells, ANOVA p<0.001, Scheffe p<0.05, SOD1WT 10 mM NMDA vs SOD1KO 10 mM NMDA)
SOD1 has a protective role in the retina against NMDA-induced neurotoxicity.
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