title: The effects and underlying mechanisms of S-allyl l-cysteine treatment of the retina after ischemia/reperfusion.
abstract: OBJECTIVE
  Retinal ischemia-associated ocular disorders are vision-threatening. The aim of the present study was to examine whether S-allyl l-cysteine (SAC) is able to protect against retina ischemia/reperfusion injury.
  
  
  METHODS
  In vivo, retinal ischemia in the rat was induced by raising intraocular pressure (IOP) to 120 mmHg for 60 min. In vitro, an ischemic-like insult, namely oxidative stress, was established by incubating retinal ganglion cell-5 (RGC-5) with 500 μM H(2)O(2) for 24 h. The mechanisms involved in these processes were evaluated by electrophysiology, immunohistochemistry, and molecular biological approaches.
  
  
  RESULTS
  The retinal changes caused by the high IOP were characterized by a decrease in electroretinogram b-wave amplitudes, a loss of choline acetyltransferase immunolabeling amacrine cell bodies/neuronal processes, and an upregulation of the mRNA levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelium growth factor (VEGF), and matrix metalloproteinase-9 (MMP-9). The increased protein levels of HIF-1α, VEGF, and MMP-9 were also seen in RGC-5 cells subjected to defined oxidative stress. Of clinical importance, the ischemic/ischemic-like detrimental effects were concentration-dependently (least effect at 25 μM) and/or significantly (50 and/or 100 μM) blunted when SAC was applied 15 min before retinal ischemia or ischemic-like insult, respectively.
  
  
  CONCLUSIONS
  SAC would seem to protect against retinal ischemia by acting as an antioxidant and inhibiting the upregulation of HIF-1α, VEGF, and MMP-9.
authors: Department of Pharmacology, School of Medicine, Shandong University, Jinan, Shandong, People's Republic of China.
authors: Yan-Qing
authors: YQ
authors: Chen
authors: Wynn H T
authors: WH
authors: Pan
authors: Jorn-Hon
authors: JH
authors: Liu
authors: Mi-Mi
authors: MM
authors: Chen
authors: Chi-Ming
authors: CM
authors: Liu
authors: Ming-Yang
authors: MY
authors: Yeh
authors: Shen-Kou
authors: SK
authors: Tsai
authors: Mason Shing
authors: MS
authors: Young
authors: Xiu-Mei
authors: XM
authors: Zhang
authors: Hsiao-Ming
authors: HM
authors: Chao
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D002460:Cell Line; D003545:Cysteine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D007429:Intraocular Pressure / Q000187:drug effects; D007511:Ischemia / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D012160:Retina / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D000975:Antioxidants; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; C065299:S-allylcysteine; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D003545:Cysteine