title: Protective effects of resveratrol in experimental retinal detachment.
abstract: BACKGROUND
  Oxidative stress is one of the major factors that trigger photoreceptor apoptosis. To investigate whether resveratrol, a potent antioxidant and small molecule activator of the FoxO pathway, would be neuroprotective against photoreceptor cell death in a rodent model of retinal detachment.
  
  
  METHODS
  Retinal detachment was created in adult Brown Norway rats by subretinal injection of sodium hyaluronate. The animals were treated daily with vehicle or resveratrol (20 mg/kg) intraperitoneal injection. Photoreceptor death was assessed by counting the number of apoptotic cells with TdT-dUTP terminal nick-end labeling (TUNEL) and measurement of the outer nuclear layer (ONL) thickness 3 days after RD. Changes in expression of FoxO1a, FoxO3a, and FoxO4 were analyzed by western blot. The activity of caspase 3, caspase 8, caspase 9, spectrin and their cleavage forms were studied.
  
  
  RESULTS
  Three days after retinal detachment, caspase 3, caspase 8 and caspase 9 were significantly activated in the detached retina. Spectrin cleavage products at 120 and 145 kDa were also detected. Both caspase and calpain activation are involved in apoptotic photoreceptor cell death in detached retinas. Treatment with resveratrol increases FoxO1a, FoxO3a, and FoxO4 protein expression in detached retinas only. Resveratrol treatment decreases activation of intrinsic and extrinsic caspase apoptotic pathways triggered by RD. The number of TUNEL-positive cells decreases from 1301±51 cells/mm(2) in control groups to 430±35 cells/mm(2) in treatment groups (p<0.05). Resveratrol treatment also demonstrates 59% less ONL thickness loss compared to controls.
  
  
  CONCLUSIONS
  Resveratrol treatment up-regulates the FoxO family and blocks Caspase3, 8, and 9 activation. Resveratrol has the potential to be used as a novel therapeutic agent for preventing vision loss in diseases characterized by photoreceptor detachment.
authors.affiliation: Duke Eye Center, Duke University, Durham, North Carolina, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Guorong
authors.initials: G
authors.lastname: Li
authors.forename: Jianming
authors.initials: J
authors.lastname: Qiu
authors.forename: Pedro
authors.initials: P
authors.lastname: Gonzalez
authors.forename: Pratap
authors.initials: P
authors.lastname: Challa
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D008297:Male; D010786:Photoreceptor Cells / Q000187:drug effects / Q000473:pathology; D051381:Rats; D000077185:Resveratrol; D012163:Retinal Detachment / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D051858:Forkhead Transcription Factors; D013267:Stilbenes; D020169:Caspases; D000077185:Resveratrol
references.citation: Invest Ophthalmol Vis Sci. 2010 Jun;51(6):3049-54
references.pmid: 20107181
references.citation: Biochem J. 1996 Nov 1;319 ( Pt 3):683-90
references.pmid: 8920967
references.citation: Science. 2004 Mar 26;303(5666):2011-5
references.pmid: 14976264
references.citation: Hepatology. 1995 May;21(5):1465-8
references.pmid: 7737654
references.citation: PLoS One. 2011;6(9):e24245
references.pmid: 21961034
references.citation: Apoptosis. 2012 Aug;17(8):871-9
references.pmid: 22562605
references.citation: Cell. 2007 Jan 26;128(2):325-39
references.pmid: 17254970
references.citation: Invest Ophthalmol Vis Sci. 2011 Jun 01;52(6):3825-31
references.pmid: 21310909
references.citation: Curr Neurovasc Res. 2009 Feb;6(1):70-81
references.pmid: 19355928
references.citation: Invest Ophthalmol Vis Sci. 2011 Jun 21;52(7):4395-401
references.pmid: 21345980
references.citation: J Mol Neurosci. 2013 Jul;50(3):504-13
references.pmid: 23435869
references.citation: Antioxid Redox Signal. 2005 May-Jun;7(5-6):752-60
references.pmid: 15890021
references.citation: Invest Ophthalmol Vis Sci. 2003 Mar;44(3):1262-7
references.pmid: 12601057
references.citation: Inhal Toxicol. 2009 Oct;21(12):979-84
references.pmid: 19555232
references.citation: Am J Ophthalmol. 2005 Apr;139(4):605-10
references.pmid: 15808154
references.citation: J Biol Chem. 2011 Mar 4;286(9):7468-78
references.pmid: 21159781
references.citation: Rev Neurol. 2012 Mar 16;54(6):349-56
references.pmid: 22403148
references.citation: J Cell Sci. 2007 Aug 1;120(Pt 15):2479-87
references.pmid: 17646672
references.citation: CNS Neurosci Ther. 2013 Sep;19(9):675-81
references.pmid: 23731528
references.citation: Genes Nutr. 2011 May;6(2):161-9
references.pmid: 21541654
references.citation: Invest Ophthalmol Vis Sci. 2006 Dec;47(12):5469-75
references.pmid: 17122138
references.citation: J Physiol Pharmacol. 2012 Jun;63(3):293-301
references.pmid: 22791644
references.citation: Nature. 2006 Nov 16;444(7117):337-42
references.pmid: 17086191
references.citation: Adv Exp Med Biol. 2012;723:547-52
references.pmid: 22183376
references.citation: Exp Cell Res. 2012 Jul 1;318(11):1278-84
references.pmid: 22366479
references.citation: Biochem J. 1984 Oct 1;223(1):47-51
references.pmid: 6093770
references.citation: Diabetes. 2010 Jul;59(7):1825-35
references.pmid: 20424226