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

Neuroreport. 2011 Sep 14;22(13):633-6. doi: 10.1097/WNR.0b013e32834959c5.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Calpain / antagonists & inhibitors*
  • Ischemia / drug therapy*
  • Ischemia / physiopathology
  • Leupeptins / pharmacology
  • Leupeptins / therapeutic use*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Retinal Diseases / drug therapy*
  • Retinal Diseases / physiopathology
  • Retinal Vessels / drug effects*
  • Retinal Vessels / physiopathology


  • CYLA (leupeptin)
  • Leupeptins
  • Calpain