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D. C. Fernandez, M. Bordone, H. J. Aldana Marcos, M. Chianelli, R. Rosenstein; Retinal Neuroprotection Against Ischemia/Reperfusion Damage Induced by Postconditioning. Invest. Ophthalmol. Vis. Sci. 2009;50(13):376.
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Retinal ischemia could provoke blindness. There is no effective treatment against retinal ischemic damage. We investigated whether brief intermittent ischemia applied during the onset of reperfusion (i.e., postconditioning) protects the retina from ischemia/reperfusion damage.
Ischemia was induced in male Wistar rats by increasing intraocular pressure (120 mm Hg for 40 min). Five minutes after ischemia, animals underwent 7 cycles of 1min/1min ischemia/reperfusion. In other experiments, 7 ischemia/reperfusion cycles were applied 10, 30, 60 min or 24 h after ischemia. A group of animals received intraperitoneal injections of cycloheximide 1 min before or 6 h after postconditioning, whereas another group was injected with aminoguanidine (an inducible nitric oxide synthase inhibitor) 1 min before and 6 h after postconditioning. Seven or 14 days after ischemia, animals were subjected to electroretinography and histological and immunohistochemical analysis.
Ischemia induced a significant decrease in scotopic ERG a- and b-wave amplitude. The ischemic-induced decrease in both a- and b-wave amplitude was significantly reduced by the application of 7 cycles of ischemia/reperfusion applied 5 min after ischemia. A significant increase in glial fibrillary acidic protein (GFAP) levels in Müller cells was observed in ischemic retinas, which was not evident in postconditioned retinas. Moreover, 7 cycles of ischemia/reperfusion applied 5, 10, 30 and 60 min (but not 24 h) after ischemia afforded significant functional and histological protection against ischemic injury, in a time post-ischemia- dependent manner. Protection induced by postconditioning was reversed by cycloheximide (injected 1 min before but not 6 h after postconditioning) and aminoguanidine.
For the first time, these results indicate that postconditioning significantly protected retinal function and histology from ischemia/reperfusion injury, through a mechanism which involves the novo synthesis of protein(s), and inducible NOS activity.
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