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A. Obolensky, E. Berenshtein, E. Banin, M. Chevion; Retinal Ischemic Preconditioning: Role of Ferritin and Redox–Associated Proteins . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1632.
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Purpose: To evaluate the roles of ferritin and redox–associated proteins in a rat model of retinal ischemic preconditioning (IPC). Methods: 42 Sprague–Dawley rats were used. Transient retinal ischemia was induced by occlusion of the blood vessels at the base of the optic nerve in one eye, with the fellow eye serving as an internal control. Four experimental groups were included: Control; IPC alone (7min of ischemia); Ischemia alone (1 hour), and IPC+Ischemia (IPC for 7min and 1h ischemia 40±2h later). To validate the effect and to study the mechanisms of IPC, electrophysiological (electroretinogram – ERG), histological, and biochemical techniques including ELISA, HPLC and western blot (WB) were used. Results: ERG recordings performed 24h after a transient 1h episode of ischemia revealed total loss of retinal electrophysiological function. IPC markedly protected the retina from this ischemic injury, and ERG a– and b–waves amplitudes were maintained at 80–97% of fellow (non–ischemic) eye values. Histological findings support the protective effect of IPC: sections obtained one week after exposure to 1h of ischemia showed severe loss of cells in the outer and inner nuclear layers, as well as inflammation and signs of degradation. These were largely prevented by IPC. Ferritin (Ft) level determined by ELISA significantly decreased after 1h ischemia alone. In contrast, when ischemia was preceded by IPC, a marked increase of Ft levels was observed. Interestingly, a prominent two–fold elevation of Ft content was also observed in both treated and fellow eyes of animals subjected to IPC alone. In addition, marked elevation of Thioredoxin (Trx) was observed in ischemia–alone retinas, which was largely prevented by IPC. Reductions in Methionine Sulfoxide Reductase (Msr) activity (estimated by HPLC) and reductions in the levels of Thioredoxin Reductase (TrxR; measured by WB) that were induced by 1h ischemia alone were also partially reversed by IPC, though to a lesser extent. Conclusions: IPC is highly effective in reducing functional and structural retinal ischemic injury. The protective effect may be associated with accumulation of Ft and with modulation of the levels and activity of a number of redox–associated proteins including Msr, Trx and TrxR.
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