title: Nimodipine inhibits N-methyl-N-nitrosourea-induced retinal photoreceptor apoptosis in vivo.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang- 110 001, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Gui Yuan
authors.initials: GY
authors.lastname: Sun
mesh_terms: D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D004596:Electroretinography; D005260:Female; D005434:Flow Cytometry; D007274:Injections, Intraperitoneal; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008770:Methylnitrosourea / Q000633:toxicity*; D008854:Microscopy, Electron; D009553:Nimodipine / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000378:metabolism; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects* / Q000648:ultrastructure; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012162:Retinal Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000477:Alkylating Agents; C494828:Bax protein, rat; D002121:Calcium Channel Blockers; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D009553:Nimodipine; D008770:Methylnitrosourea; D010727:Phosphoric Diester Hydrolases; D053148:Caspase 3
keywords: N-methyl-N-nitrosourea; Nimodipine; retinal degeneration