title: The neuroprotective effect of resveratrol on retinal ganglion cells after optic nerve transection.
abstract: OBJECTIVE
  This study aimed to investigate the neuroprotective effect of resveratrol in an optic nerve transection (ONT) model and to identify the neuroprotective mechanism of resveratrol in retinal ganglion cells (RGCs).
  
  
  METHODS
  ONT and retrograde labeling were performed in Sprague-Dawley rats. Various concentrations of resveratrol were injected intravitreally immediately after ONT. The number of labeled RGCs was determined at 1 and 2 weeks after ONT. The effect of resveratrol and sirtinol (a sirtuin 1 inhibitor) co-injection was investigated. RGC-5 cells were cultured and treated with staurosporine to induce differentiation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to evaluate the effect of resveratrol on RGC-5 cell survival under serum-free conditions. RGC-5 cells were cultured with sirtinol to investigate the neuroprotective mechanism of resveratrol.
  
  
  RESULTS
  A dose-response relationship was observed between resveratrol and RGC survival. A single intravitreal injection of resveratrol was neuroprotective in RGCs at 1 week after ONT (p<0.01). Repeated intravitreal injection of resveratrol showed a neuroprotective effect at 2 weeks after ONT (p<0.01). However, co-injection of resveratrol and sirtinol diminished the neuroprotective effect of resveratrol (p<0.05). The neuroprotective effect of resveratrol was observed in RGC-5 cells under serum-free conditions, and sirtinol diminished this neuroprotective effect.
  
  
  CONCLUSIONS
  Resveratrol exerts its neuroprotective effect on RGCs via activation of the sirtuin 1 pathway in an ONT model. This finding demonstrates the therapeutic potential of resveratrol in treating optic nerve diseases.
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea. xcski@hanmail.net
authors.forename: Seok Hwan
authors.initials: SH
authors.lastname: Kim
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Yu Jeong
authors.initials: YJ
authors.lastname: Kim
authors.forename: Ki Ho
authors.initials: KH
authors.lastname: Park
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D016895:Culture Media, Serum-Free; D004305:Dose-Response Relationship, Drug; D008297:Male; D009284:Naphthols / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020221:Optic Nerve Injuries; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D056564:Sirtuin 1 / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D001549:Benzamides; D016895:Culture Media, Serum-Free; D009284:Naphthols; D018696:Neuroprotective Agents; D013267:Stilbenes; C439060:sirtinol; D056564:Sirtuin 1; D000077185:Resveratrol
references.citation: Invest Ophthalmol Vis Sci. 2012 May 31;53(6):3241-9
references.pmid: 22491413
references.citation: Nature. 2003 Sep 11;425(6954):191-6
references.pmid: 12939617
references.citation: Mol Cell. 2004 Mar 12;13(5):627-38
references.pmid: 15023334
references.citation: Cell. 2001 Oct 19;107(2):137-48
references.pmid: 11672522
references.citation: Invest Ophthalmol Vis Sci. 2007 Aug;48(8):3602-9
references.pmid: 17652729
references.citation: Exp Eye Res. 2010 Apr;90(4):528-34
references.pmid: 20114044
references.citation: Brain Res Mol Brain Res. 2000 Dec 28;85(1-2):144-50
references.pmid: 11146116
references.citation: PLoS One. 2008 Jun 04;3(6):e2264
references.pmid: 18523577
references.citation: Nature. 2002 Sep 19;419(6904):316-21
references.pmid: 12239572
references.citation: Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1632-6
references.pmid: 8127857
references.citation: Brain Res. 1993 Feb 5;602(2):304-17
references.pmid: 8448673
references.citation: Invest Ophthalmol Vis Sci. 2009 Sep;50(9):4267-72
references.pmid: 19443730
references.citation: Neuron. 1989 Jun;2(6):1525-34
references.pmid: 2697237
references.citation: Exp Neurol. 1999 Aug;158(2):366-81
references.pmid: 10415143
references.citation: Invest Ophthalmol Vis Sci. 2006 Jan;47(1):427-38
references.pmid: 16384993
references.citation: Invest Ophthalmol Vis Sci. 2009 Aug;50(8):3562-72
references.pmid: 19407027
references.citation: Neuroscience. 2009 Mar 31;159(3):993-1002
references.pmid: 19356683
references.citation: Eur J Neurosci. 1997 Aug;9(8):1763-72
references.pmid: 9283831
references.citation: Restor Neurol Neurosci. 2001;19(1-2):19-27
references.pmid: 12082226
references.citation: Nat Rev Drug Discov. 2006 Jun;5(6):493-506
references.pmid: 16732220
references.citation: Cell. 2001 Oct 19;107(2):149-59
references.pmid: 11672523
references.citation: J Neurochem. 2007 Aug;102(3):922-30
references.pmid: 17442051
references.citation: Science. 2004 Aug 13;305(5686):1010-3
references.pmid: 15310905
references.citation: Curr Neurovasc Res. 2009 Feb;6(1):70-81
references.pmid: 19355928
references.citation: Eur J Neurosci. 2007 Aug;26(4):828-42
references.pmid: 17714182
references.citation: Int J Mol Med. 2005 Aug;16(2):237-43
references.pmid: 16012755
references.citation: Mol Nutr Food Res. 2005 May;49(5):482-94
references.pmid: 15779067
references.citation: Drug Metab Dispos. 2004 Dec;32(12):1377-82
references.pmid: 15333514
references.citation: Neurosci Lett. 2007 Jun 13;420(2):133-7
references.pmid: 17531385
references.citation: FEBS Lett. 1999 Jun 25;453(3):361-4
references.pmid: 10405176
references.citation: Nat Rev Cancer. 2009 Feb;9(2):123-8
references.pmid: 19132007
references.citation: Nature. 2004 Aug 5;430(7000):686-9
references.pmid: 15254550
references.citation: Invest Ophthalmol Vis Sci. 2008 Aug;49(8):3535-43
references.pmid: 18441302
references.citation: Mol Neurobiol. 2010 Jun;41(2-3):375-83
references.pmid: 20306310
references.citation: J Neurosci Res. 2008 Oct;86(13):2943-51
references.pmid: 18521932
references.citation: J Biol Chem. 2005 Nov 11;280(45):37377-82
references.pmid: 16162502
references.citation: Nat Genet. 2005 Apr;37(4):349-50
references.pmid: 15793589
references.citation: J Biol Chem. 2005 Dec 2;280(48):40364-74
references.pmid: 16183991