A novel calpain inhibitor for treatment of transient retinal ischemia in the rat

作者:David Joel*; Melamud Aleksandr; Kesner Leo; Roth Steven; Rosenbaum Pearl S; Barone Frank C; Popp Sussana; Hassen Getaw Worku; Stracher Alfred; Rosenbaum Daniel M
来源:NeuroReport, 2011, 22(13): 633-636.
DOI:10.1097/WNR.0b013e32834959c5

摘要

After an acute ischemia/reperfusion of the rat retina, the activation of cytotoxic proteases, including calpain, results in necrosis and apoptosis of retinal ganglion cells resulting in their degeneration. Using a systemically administered calpain inhibitor that crosses the blood-retinal barrier would provide for novel systemic intervention that protects the retina from acute injury and loss of function. Herein, we study a novel calpain peptide inhibitor, cysteic-leucyl-argininal (CYLA), in an in-vivo rat model of retinal ischemia to determine functional protection using electroretinography. The CYLA prodrug was administered intraperitoneally before and/or after ischemia-reperfusion at concentrations of 20-40 mg/kg. We found that administering 20 mg/kg of CYLA only after ischemia provides significant preservation of retinal function.

  • 出版日期2011-9-14