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T. Kurokawa, N. Katai, K. Ohta, J. Arai, N. Yoshimura; Activation of NFB and Protective Effects of Pyrrolidine Dithiocarbamate on Retinal Ischemia–reperfusion Injury in Rats . Invest. Ophthalmol. Vis. Sci. 2004;45(13):656.
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Purpose:Retinal ischemia–reperfusion induces apoptosis of retinal neurons. The purpose of this study was to determine whether pyrrolidine dithiocarbamate (PDTC), an antioxidant/NFΚB inhibitor, had a protective effect against the injury induced by retinal ischemia–reperfusion. The time course of NFΚB activation in the early phase of reperfusion and the change of NFΚB activation after administration of PDTC were also studied. Methods: Adult female Sprague–Dawley rats were injected intraperitoneally with 60 and 200 mg/kg PDTC at 12 hours and again just before the ischemia. The control rats received the vehicle. The retinal ischemia was induced by increasing the intraocular pressure to 110 mmHg for 45 minutes. Electroretinograms (ERGs) were recorded before ischemia and on days 7, 14, and 28 after reperfusion, and the eyes were enucleated on day 28 for histological study. The amplitudes of ERG a– and b–waves, the number of cells in the retinal ganglion cell layer (RGCL) and inner retinal thickness were compared among the three groups. To investigate the time course of NFΚB activation in early phase of reperfusion, phosphorylation of IΚB was evaluated by western blot analysis by six hours after reperfusion. The change of phosphorylation of IΚB after PDTC administration was also studied at three hours after reperfusion. Results: The a–wave amplitudes of the ERG were reduced and not significantly protected by PDTC administration. However, the b–waves of rats treated with 200 mg/kg of PDTC were significantly larger than that of control animals at each time point (P < 0.01). The number of cells in the RGCL, and the inner retinal layer was significantly thicker in the PDTC–treated group than in the vehicle–treated control (P < 0.01). Phosphorylation of IΚB started fifteen minutes after reperfusion and peaked at three hours, and this phosphorylation was suppressed by PDTC. Conclusions: This study shows that PDTC protects retinas against transient ischemia by down–modulating NFΚB.
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