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

Abstract

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.

• Authors: Joel David, Aleksandr Melamud, Leo Kesner, Steven Roth, Pearl S Rosenbaum, Frank C Barone, Sussana Popp, Getaw Worku Hassen, Alfred Stracher, Daniel M Rosenbaum
• Journal: Neuroreport (Neuroreport) Vol. 22 Issue 13 Pg. 633-6 (Sep 14 2011) ISSN: 1473-558X [Electronic] England
• PMID: 21841454 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: 2011 Wolters KluwerHealth | Lippincott Williams & Wilkins.

Chemical References

• CYLA (leupeptin)
• Leupeptins
• Calpain

Topics

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