title: 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.affiliation: Department of Neurology, SUNY Downstate Medical Center, Brooklyn, NY 11203, USA. jsdavid@gmail.com
authors.forename: Joel
authors.initials: J
authors.lastname: David
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Melamud
authors.forename: Leo
authors.initials: L
authors.lastname: Kesner
authors.forename: Steven
authors.initials: S
authors.lastname: Roth
authors.forename: Pearl S
authors.initials: PS
authors.lastname: Rosenbaum
authors.forename: Frank C
authors.initials: FC
authors.lastname: Barone
authors.forename: Sussana
authors.initials: S
authors.lastname: Popp
authors.forename: Getaw Worku
authors.initials: GW
authors.lastname: Hassen
authors.forename: Alfred
authors.initials: A
authors.lastname: Stracher
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Rosenbaum
mesh_terms: D000818:Animals; D002154:Calpain / Q000037:antagonists & inhibitors*; D007511:Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D007976:Leupeptins / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012164:Retinal Diseases / Q000188:drug therapy* / Q000503:physiopathology; D012171:Retinal Vessels / Q000187:drug effects* / Q000503:physiopathology
chemical_list: C539819:CYLA (leupeptin); D007976:Leupeptins; D002154:Calpain