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  • Title: Nimodipine inhibits N-methyl-N-nitrosourea-induced retinal photoreceptor apoptosis in vivo.
    Author: Wang D, Wang Z, Li Y, Chen X, Sun GY.
    Journal: Indian J Pharmacol; 2013; 45(2):149-54. PubMed ID: 23716891.
    Abstract:
    PURPOSE: The purpose of the present study was to investigate the effect of nimodipine (NMD), a calcium channel blocker, on N-methyl-N-nitrosourea (MNU)-induced retinal degeneration. MATERIALS AND METHODS: 60 mg/kg MNU was given intraperitoneally to 6-week-old female Sprague-Dawley rats, and NMD was injected intraperitoneally for up to 5 days after MNU. The effect of NMD was evaluated by electron microscopy and electroretinography (ERG). Proteins of Bax, Bcl-2, Caspase-3, and mitochondrial membrane potential (MMP) were analyzed with flow cytometry. The expressions of phosphodiesterase (PDE) and Caspase-3 were detected by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: The apparent preservation of NMD to the photoreceptor cell was demonstrated by electron microscopy. After NMD treatment, both a- and b-waves of ERG were significantly higher compared with the control group, and had a protective effect on MNU-damaged retinal ERG. Flow cytometric assays showed that NMD decreased the level of Bax and Caspase-3 and increased the activity of Bcl-2 in retina. NMD significantly restored the mitochondrial membrane potential (MMP). RT-PCR analysis demonstrated that NMD treatment significantly decreased mRNA level of Caspase-3, and mRNA level of PDE was clearly upregulated. CONCLUSIONS: These data suggest that NMD may regulate the expressions of Bax, Bcl-2, Caspases-3, and PDE, and protection on the functions of retinal cell mitochondria inhibit MNU-induced photoreceptor cell apoptosis and protect retinal function in rats.
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