title: Down-regulation of matrix metalloproteinase-9 by pyrrolidine dithiocarbamate prevented retinal ganglion cell death after transection of optic nerve in rats.
abstract: OBJECTIVE
  To investigate the effects of pyrrolidine dithiocarbamate (PDTC), a nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) inhibitor, on the expression of matrix metalloproteinases (MMP) and MMP-mediated apoptosis in retinal ganglion cells (RGCs) following the transection of the optic nerve (ON) in rats.
  
  
  METHODS
  The ON of adult male Sprague-Dawley rats was transected. The expression of MMP-2, MMP-9, and NF-κB was measured by Western blot analysis and immunohistochemical analysis following transection. In situ zymography was also performed to localize gelatinolytic activity in the retinas. PDTC was injected intravitreally immediately following transection of the ON to evaluate the effect on the expression of NF-κB and MMP as well as its anti-apoptotic effect and neuroprotective effect on RGCs.
  
  
  RESULTS
  Significant up-regulation of MMP-9, and NF-κB was observed 7 days post-transection; however, this was not observed for MMP-2. PDTC at concentrations of 0.5 mM suppressed the up-regulation of MMP-9 and NF-κB, inhibiting gelatinolytic activity in the RGC layer. Meanwhile, far fewer apoptotic RGCs were detected and more surviving RGCs were preserved in PDTC-treated retinas 7 days post-transection compared to retinas in the control group. However, this kind of neuroprotective effect was not significant at 14 days post-transection.
  
  
  CONCLUSIONS
  This study demonstrated that PDTC, mediated in part through the down-regulation of MMP-9, could contribute to delaying the death of RGCs following transection of the ON.
authors: Department of Ophthalmology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan.
authors: Ming-Hui
authors: MH
authors: Sun
authors: Kuan-Jen
authors: KJ
authors: Chen
authors: Yeou-Ping
authors: YP
authors: Tsao
authors: Ling-Yuh
authors: LY
authors: Kao
authors: Wen-Hwa
authors: WH
authors: Han
authors: Ken-Kuo
authors: KK
authors: Lin
authors: Jong-Hwei Su
authors: JH
authors: Pang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002452:Cell Count; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000187:drug effects; D009900:Optic Nerve / Q000601:surgery*; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012164:Retinal Diseases / Q000201:enzymology / Q000473:pathology* / Q000517:prevention & control; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D013859:Thiocarbamates / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D013859:Thiocarbamates; C066229:prolinedithiocarbamate; D011392:Proline; D020780:Matrix Metalloproteinase 9