Nimodipine inhibits N-methyl-N-nitrosourea-induced retinalphotoreceptor apoptosis in vivo

• Published in: Indian journal of pharmacology Vol. 45; no. 2; pp. 149 - 154
• Main Authors: Wang, Dan, Wang, Zhuo, Li, Yan, Chen, Xin, Sun, Gui
• Format: Journal Article
• Language: English
• Published: Pondicherry Medknow Publications 01.03.2013; Medknow Publications and Media Pvt. Ltd; Medknow Publications & Media Pvt. Ltd; Medknow Publications & Media Pvt Ltd
• Subjects: Care and treatment; Cellular biology; Cellular control mechanisms; Dosage and administration; Eye diseases; Nimodipine; Pharmacology; Retinal degeneration; Rodents; Testing; India; Nimodipine; N-methyl-N-nitrosourea; retinal degeneration
• ISSN: 0253-7613; 1998-3751
• DOI: 10.4103/0253-7613.108297

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.