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

David, Joela; Melamud, Aleksandra; Kesner, Leob; Roth, Stevenh; Rosenbaum, Pearl S.e,f; Barone, Frank C.a; Popp, Sussanac; Hassen, Getaw Workug; Stracher, Alfredb; Rosenbaum, Daniel M.a

doi: 10.1097/WNR.0b013e32834959c5
VISION, RETINA
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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.

aDepartment of Neurology

bDepartment of Biochemistry, SUNY Downstate Medical Center, Brooklyn

cDepartment of Physiology/Pharmacology, SUNY Downstate Medical Center, Brooklyn, NY

eDepartment of Ophthalmology and Pathology, Bronx-Lebanon Hospital Center, Bronx NY

fDepartment of Ophthalmology and Pathology, Albert Einstein College of Medicine, Bronx NY

gDepartment of Emergency Medicine, Metropolitan Hospital Center, New York Medical College, New York

hDepartment of Anesthesia and Critical Care, University of Chicago, Chicago, Illinois, USA

Correspondence to Joel S. David, SUNY Downstate Medical Center, Department of Neurology, PO Box 1213, 450 Clarkson Avenue, Brooklyn, NY 11203, USA Tel: +1 718 270 2051; fax: +1 718 270 5761; e-mail: jsdavid@gmail.com

Received May 11, 2011

Accepted May 29, 2011

© 2011 Lippincott Williams & Wilkins, Inc.