title: Inhibition of retinopathy and retinal metabolic abnormalities in diabetic rats with AREDS-based micronutrients.
abstract: OBJECTIVE
  To investigate whether the micronutrients that were shown to reduce the risk of development of age-related macular degeneration in the Age-Related Eye Disease Study (AREDS) can have the same effect on the development of diabetic retinopathy in rats, and to understand the possible mechanisms.
  
  
  METHODS
  Streptozotocin-induced diabetic rats received a powdered diet with or without supplemental micronutrients (ascorbic acid, vitamin E, beta-carotene, zinc, and copper). The retina was used after the rats had diabetes for 12 months to detect vascular histopathology and to measure the biochemical parameters and messenger RNA levels of the genes involved in oxidative and nitrative stress.
  
  
  RESULTS
  The AREDS-based micronutrients prevented a diabetes-induced increase in the number of retinal acellular capillaries. In the same rats, micronutrients inhibited increases in retinal oxidatively modified DNA and nitrotyrosine and decreases in manganese superoxide dismutase. Diabetes-induced alterations in the messenger RNA expression of mitochondrial electron transport complex III (coenzyme Q cytochrome-c reductase) and inducible nitric oxide synthase were also prevented.
  
  
  CONCLUSIONS
  Age-Related Eye Disease Study-based micronutrients inhibit the development of diabetic retinopathy in rodents by inhibiting oxidative and nitrative stress.
  
  
  CONCLUSIONS
  Micronutrients that slow down the onset and progression of age-related macular degeneration have the potential to inhibit the development of diabetic retinopathy.
authors.affiliation: Kresge Eye Institute, Wayne State University, 4717 St Antoine, Detroit, MI 48201, USA. rkowluru@med.wayne.edu
authors.forename: Renu A
authors.initials: RA
authors.lastname: Kowluru
authors.forename: Mamta
authors.initials: M
authors.lastname: Kanwar
authors.forename: Pooi-See
authors.initials: PS
authors.lastname: Chan
authors.forename: Jiang Ping
authors.initials: JP
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage; D001835:Body Weight; D003300:Copper / Q000008:administration & dosage; D003839:Deoxyadenosines / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004032:Diet; D004435:Eating; D014450:Electron Transport Complex III / Q000235:genetics / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000032:analysis; D007124:Immunoenzyme Techniques; D008297:Male; D018977:Micronutrients / Q000008:administration & dosage*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012171:Retinal Vessels / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014810:Vitamin E / Q000008:administration & dosage; D015034:Zinc Oxide / Q000008:administration & dosage; D019207:beta Carotene / Q000008:administration & dosage
chemical_list: D001205:Ascorbic Acid; D003300:Copper; D003839:Deoxyadenosines; D014450:Electron Transport Complex III; D006442:Glycated Hemoglobin; D018977:Micronutrients; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger; D013482:Superoxide Dismutase; D014443:Tyrosine; D014810:Vitamin E; D015034:Zinc Oxide; D019207:beta Carotene; C436623:8-hydroxy-2'-deoxyadenosine; C002744:3-nitrotyrosine; C030973:cupric oxide
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17525-30
references.pmid: 17088544
references.citation: Diabetes. 2004 Dec;53(12):3233-8
references.pmid: 15561955
references.citation: Invest Ophthalmol Vis Sci. 1995 Nov;36(12):2368-80
references.pmid: 7591626
references.citation: Invest Ophthalmol Vis Sci. 1993 May;34(6):2092-6
references.pmid: 8491559
references.citation: Am J Clin Nutr. 2004 May;79(5):865-73
references.pmid: 15113727
references.citation: Arch Ophthalmol. 2007 Sep;125(9):1225-32
references.pmid: 17846363
references.citation: Endocr Res. 2005;31(3):199-212
references.pmid: 16392622
references.citation: Nat Med. 2003 Mar;9(3):294-9
references.pmid: 12592403
references.citation: Mol Aspects Med. 2005 Aug-Oct;26(4-5):268-98
references.pmid: 16112185
references.citation: Diabetes. 1987 Jul;36(7):808-12
references.pmid: 3556280
references.citation: Exp Mol Pathol. 2003 Aug;75(1):95-108
references.pmid: 12834631
references.citation: Physiol Rev. 2007 Jan;87(1):315-424
references.pmid: 17237348
references.citation: Nitric Oxide. 2000 Dec;4(6):590-6
references.pmid: 11139367
references.citation: Toxicol Lett. 2003 Apr 11;140-141:113-24
references.pmid: 12676457
references.citation: N Engl J Med. 1993 Sep 30;329(14):977-86
references.pmid: 8366922
references.citation: Curr Opin Chem Biol. 2002 Apr;6(2):171-80
references.pmid: 12039001
references.citation: Diabetes. 1994 Sep;43(9):1122-9
references.pmid: 8070612
references.citation: Am J Clin Nutr. 2007 Jul;86(1):180-8
references.pmid: 17616779
references.citation: Free Radic Biol Med. 2007 May 15;42(10):1481-6
references.pmid: 17448894
references.citation: Nutr Metab (Lond). 2007 Apr 16;4:8
references.pmid: 17437639
references.citation: Diabetes Care. 1999 Aug;22(8):1245-51
references.pmid: 10480765
references.citation: Diabetes. 2001 Aug;50(8):1938-42
references.pmid: 11473058
references.citation: Curr Eye Res. 1994 Dec;13(12):863-7
references.pmid: 7720392
references.citation: Free Radic Biol Med. 1997;22(4):587-92
references.pmid: 9013121
references.citation: Expert Opin Investig Drugs. 2001 Sep;10(9):1665-76
references.pmid: 11772276
references.citation: Invest Ophthalmol Vis Sci. 2006 Apr;47(4):1594-9
references.pmid: 16565397
references.citation: Diabetes. 2007 Feb;56(2):337-45
references.pmid: 17259377
references.citation: Arch Ophthalmol. 2007 May;125(5):671-9
references.pmid: 17502507
references.citation: Invest Ophthalmol Vis Sci. 2008 Apr;49(4):1645-51
references.pmid: 18385086
references.citation: Invest Ophthalmol Vis Sci. 2007 Aug;48(8):3805-11
references.pmid: 17652755
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: Arch Ophthalmol. 2006 Jul;124(7):1038-45
references.pmid: 16832030
references.citation: Toxicol Appl Pharmacol. 2004 Dec 1;201(2):149-55
references.pmid: 15541754
references.citation: Am J Epidemiol. 2003 Aug 1;158(3):225-33
references.pmid: 12882944
references.citation: Free Radic Res. 2003 Nov;37(11):1169-80
references.pmid: 14703729
references.citation: Diabetes. 2005 Jun;54(6):1615-25
references.pmid: 15919781
references.citation: Exp Eye Res. 2006 Oct;83(4):807-16
references.pmid: 16750827
references.citation: Diabetologia. 2007 Sep;50(9):1987-1996
references.pmid: 17583794