TY - JOUR T1 - Calpain Inhibitor Protects Cells against Light-Induced Retinal Degeneration JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 645 LP - 652 DO - 10.1124/jpet.110.171298 VL - 335 IS - 3 AU - Shunsuke Imai AU - Masamitsu Shimazawa AU - Tomohiro Nakanishi AU - Kazuhiro Tsuruma AU - Hideaki Hara Y1 - 2010/12/01 UR - http://jpet.aspetjournals.org/content/335/3/645.abstract N2 - Calpains are activated by excessive light exposure and related to retinal degeneration. We investigated the protective effects of ((1S)-1-((((1S)-1-benzyl-3-cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-methylbutyl)carbamic acid 5-methoxy-3-oxapentyl ester (SNJ-1945), a calpain inhibitor, against light-induced retinal degeneration in mice. SNJ-1945 was orally administrated at doses of 100 and 200 mg/kg at 30 min before and just after light exposure. Light-induced calpain activation was evaluated by using proteolysis of α-spectrin and p35 (a neuron-specific activator for cyclin-dependent kinase 5). The effects of SNJ-1945 against light-induced retinal damage were examined by the thickness of the outer nuclear layer (ONL). Photoreceptor apoptosis was assessed by counting terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells in ONL. Retinal functions were measured in terms of a- and b-wave amplitudes by using an electroretinogram. As the mechanism of SNJ-1945, caspase-3/7 measurement was carried out. SNJ-1945 inhibited the proteolysis of α-spectrin and p35 by light exposure and presented a decrease in the numbers of TUNEL-positive cells and ONL atrophy. Furthermore, SNJ-1945 presented a decrease in a- and b-wave amplitude and caspase-3/7 activation induced by light exposure. These findings suggest that the activation of calpain plays a pivotal role in photoreceptor degeneration by light exposure, and SNJ-1945 may be a candidate for effectively treating diseases related to photoreceptor degeneration. ER -