title: S-allyl L-cysteine protects the retina against kainate excitotoxicity in the rat.
abstract: Excitotoxicity has been proposed to play a pivotal role in retinal ischemia. Retinal ischemia-associated ocular disorders are vision threatening. The aim was to also examine whether and how S-allyl L-cysteine (SAC) can protect the retina against kainate excitotoxicity. In vivo retinal excitotoxicity was induced by an intravitreous injection of 100 μM kainate into a Wistar rat eye for 1 day. The management and mechanisms involved in the processes were evaluated by electrophysiology, immunohistochemistry, histopathology, and various biochemical approaches. In the present study, the cultured retinal cells were shown to possess kainate receptors. The defined retinal excitotoxic changes were characterized by a decrease in electroretinogram (ERG) b-wave amplitudes, a loss of the fluorogold retrograde labeled retinal ganglion cells (RGCs), an increase in the apoptotic cells in the RGC layer, and an increase in vimentin or glial fibrillary acidic protein (GFAP) immunoreactivity, a marker for Müller cells. An up-regulation in the mRNA levels of inducible nitric oxide synthase (iNOS) and matrix metalloproteinases-9 (MMPs-9) was also detected in the retina subjected to kainate excitoxicity. Importantly, the excitotoxicity-induced alterations were significantly blunted when 100 μM SAC and/or the kainate receptor antagonist CNQX was applied. Conclusively, SAC would seem to protect the retina against kainate excitotoxicity via an inhibition of the up-regulation of iNOS and MMP-9 as well as a modulation of glial activation and apoptosis.
authors.affiliation: Department of Ophthalmology, Cheng Hsin General Hospital, Taipei, Taiwan, R. O. C. , Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, R.O.C. , Department of Chinese Medicine, School of Chinese Medicine, China Medical University, Taichung, Taiwan, R. O. C.
authors.forename: Hsiao-Ming
authors.initials: HM
authors.lastname: Chao
authors.forename: Ing-Ling
authors.initials: IL
authors.lastname: Chen
authors.forename: Jorn-Hon
authors.initials: JH
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D003864:Depression, Chemical; D004596:Electroretinography / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009457:Neuroglia / Q000473:pathology; D018696:Neuroprotective Agents; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects; D014746:Vimentin / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D014746:Vimentin; C065299:S-allylcysteine; D052247:Nitric Oxide Synthase Type II; D020780:Matrix Metalloproteinase 9; D003545:Cysteine; D007608:Kainic Acid