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D. M. Rosenbaum, J. David, A. Melamud, L. Kesner, P. S. Rosenbaum, F. C. Barone, A. Stracher; A Novel Calpain Inhibitor for the Treatment of Transient Retinal Ischemia in the Rat. Invest. Ophthalmol. Vis. Sci. 2009;50(13):378.
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Calpain mediated proteolysis has been demonstrated to play a role in a variety of retinal degenerative disorders. The purpose of this study was to determine if a novel calpain inhibitor (Neurodur) that has demonstrated protection from injury in other models of CNS injury would preserve function in a rodent model of transient retinal ischemia-reperfusion.
Retinal ischemia-reperfusion injury was performed on Sprague-Dawley rats using the high intraocular pressure method. Animals received systemic (IP; 7.5-30 mg/kg) injections of the calpain inhibitor either prior to and after, or just after the onset of 45 minutes of ischemia. Electroretinography (ERG) was performed 7 days following ischemia to assess functional outcome.
Systemic treatment with the calpain inhibitor resulted in significant preservation of retinal function as assessed by the ERG. Combined pre- and post-drug administration produced a "U-shaped" dose-response curve with significant (p<0.05) preservation of ERG/function. Furthermore, animals treated only 3 hr after the onset of ischemia exhibited significant (p<0.05) preservation of function at 15mg/kg (43%) and 30 mg/kg (35%).
The results of these studies suggest that the activation of calcium dependent proteases plays a role in retinal neurodegeneration following ischemia-reperfusion injury. Systemic administration of the novel calpain inhibitor, Neurodur, provides significant protection of the retina. Strategies aimed at inhibiting calpain offer the potential for clinically relevant treatments in retinal disorders where ischemia plays a pathological role.
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