title: Diabetes changes the levels of ionotropic glutamate receptors in the rat retina.
abstract: OBJECTIVE
  Diabetic retinopathy (DR) is a leading cause of vision loss and blindness among adults between the age 20 to 74. Changes in ionotropic glutamate receptor subunit composition can affect retinal glutamatergic neurotransmission and, therefore, contribute to visual impairment. The purpose of this study was to investigate whether diabetes leads to changes in ionotropic glutamate receptor subunit expression at the protein and mRNA level in the rat retina.
  
  
  METHODS
  Changes in the expression of ionotropic glutamate receptor subunits were investigated at the mRNA and protein levels in retinas of streptozotocin (STZ)-induced diabetic and age-matched control rats. Animals were euthanized one, four and 12 weeks after the onset of diabetes. Retinal protein extracts were prepared, and the receptor subunit levels were assessed by western blotting. Transcript levels were assessed by real-time quantitative PCR.
  
  
  RESULTS
  Transcript levels of most ionotropic glutamate receptor subunits were not significantly changed in the retinas of diabetic rats, as compared to age-matched controls but protein levels of alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA), kainate, and N-methyl-D-aspartic acid receptors (NMDA) receptors were found to be altered.
  
  
  CONCLUSIONS
  The results provide evidence that diabetes affects the retinal content of ionotropic glutamate receptor subunits at the protein level. The possible implications of these changes on retinal physiology and visual impairment in DR are discussed.
authors.affiliation: Department of Zoology, University of Coimbra, Center for Neuroscience and Cell Biology, Coimbra, Portugal. asantiago@fmed.uc.pt
authors.forename: Ana R
authors.initials: AR
authors.lastname: Santiago
authors.forename: Joana M
authors.initials: JM
authors.lastname: Gaspar
authors.forename: Filipa I
authors.initials: FI
authors.lastname: Baptista
authors.forename: Armando J
authors.initials: AJ
authors.lastname: Cristóvão
authors.forename: Paulo F
authors.initials: PF
authors.lastname: Santos
authors.forename: Willem
authors.initials: W
authors.lastname: Kamphuis
authors.forename: António F
authors.initials: AF
authors.lastname: Ambrósio
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D017470:Receptors, Glutamate / Q000235:genetics* / Q000378:metabolism*; D018092:Kainic Acid Receptors / Q000235:genetics / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000378:metabolism* / Q000473:pathology*
chemical_list: D001786:Blood Glucose; D021122:Protein Subunits; D012333:RNA, Messenger; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate
references.citation: Diabetes. 1997 May;46(5):841-6
references.pmid: 9133553
references.citation: Diabetes Care. 1987 Nov-Dec;10(6):777-81
references.pmid: 3501362
references.citation: Trends Neurosci. 1993 Sep;16(9):359-65
references.pmid: 7694406
references.citation: J Neurosci Res. 1998 Oct 15;54(2):273-81
references.pmid: 9788286
references.citation: Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):1797-802
references.pmid: 8700838
references.citation: Prog Neurobiol. 1998 Apr;54(5):581-618
references.pmid: 9550192
references.citation: J Neurocytol. 2000 Oct;29(10):729-42
references.pmid: 11387547
references.citation: Arch Ophthalmol. 1997 Sep;115(9):1161-6
references.pmid: 9298058
references.citation: Prog Retin Eye Res. 1999 Nov;18(6):765-810
references.pmid: 10530751
references.citation: Invest Ophthalmol Vis Sci. 2005 Jun;46(6):2210-8
references.pmid: 15914643
references.citation: Diabetes Metab Res Rev. 2001 Jan-Feb;17(1):12-8
references.pmid: 11241887
references.citation: Invest Ophthalmol Vis Sci. 2004 Jan;45(1):330-41
references.pmid: 14691192
references.citation: Arch Ophthalmol. 1985 Jan;103(1):51-4
references.pmid: 3977675
references.citation: Genome Biol. 2002 Jun 18;3(7):RESEARCH0034
references.pmid: 12184808
references.citation: Neuropharmacology. 1999 May;38(5):635-44
references.pmid: 10340301
references.citation: Int J Neurosci. 2004 Mar;114(3):391-401
references.pmid: 14754663
references.citation: Brain Res. 1999 Dec 4;849(1-2):34-44
references.pmid: 10592285
references.citation: J Neurosci. 1995 Oct;15(10):6509-20
references.pmid: 7472413
references.citation: Eur J Pharmacol. 2004 Apr 19;490(1-3):177-86
references.pmid: 15094084
references.citation: Neurochem Int. 2001 Apr;38(5):385-90
references.pmid: 11222918
references.citation: Eye (Lond). 2002 May;16(3):242-60
references.pmid: 12032713
references.citation: Arch Ophthalmol. 1986 Feb;104(2):225-8
references.pmid: 3484948
references.citation: Nature. 2002 Feb 14;415(6873):793-8
references.pmid: 11823786
references.citation: Invest Ophthalmol Vis Sci. 2003 Oct;44(10):4451-6
references.pmid: 14507892
references.citation: J Neurosci. 1992 Mar;12(3):1010-23
references.pmid: 1372042
references.citation: Brain Res. 2008 Mar 10;1198:153-9
references.pmid: 18258217
references.citation: Curr Eye Res. 2002 Dec;25(6):327-31
references.pmid: 12789538
references.citation: Exp Eye Res. 2006 Oct;83(4):849-57
references.pmid: 16780836
references.citation: Clin Exp Ophthalmol. 2000 Feb;28(1):3-8
references.pmid: 11345341
references.citation: Diabetologia. 1999 Jun;42(6):693-701
references.pmid: 10382589
references.citation: Invest Ophthalmol Vis Sci. 2006 Sep;47(9):4130-7
references.pmid: 16936133
references.citation: Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10499-503
references.pmid: 1438239
references.citation: Diabetes. 1998 May;47(5):815-20
references.pmid: 9588455
references.citation: Brain Res. 2004 Feb 6;997(2):207-21
references.pmid: 14706873
references.citation: Neurochem Int. 2006 May-Jun;48(6-7):453-8
references.pmid: 16513217
references.citation: J Biol Chem. 1994 Jul 1;269(26):17367-70
references.pmid: 7545935
references.citation: Brain Res Mol Brain Res. 2005 May 20;136(1-2):275-81
references.pmid: 15893611
references.citation: Annu Rev Neurosci. 1994;17:31-108
references.pmid: 8210177
references.citation: Br J Ophthalmol. 2001 Oct;85(10):1252-9
references.pmid: 11567974
references.citation: J Neurophysiol. 2008 Jan;99(1):122-32
references.pmid: 18003876
references.citation: J Neurosci. 1999 Nov 1;19(21):9218-27
references.pmid: 10531425
references.citation: Science. 1990 Sep 28;249(4976):1580-5
references.pmid: 1699275
references.citation: Invest Ophthalmol Vis Sci. 2002 Sep;43(9):3109-16
references.pmid: 12202536
references.citation: Nature. 1998 May 28;393(6683):377-81
references.pmid: 9620802
references.citation: Mol Vis. 2005 Sep 01;11:688-96
references.pmid: 16163266
references.citation: Invest Ophthalmol Vis Sci. 2004 Sep;45(9):3259-65
references.pmid: 15326149
references.citation: J Neurosci. 1995 Oct;15(10):6498-508
references.pmid: 7472412
references.citation: Eur J Neurosci. 2000 Aug;12(8):2812-22
references.pmid: 10971623
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2003 Apr;27(2):283-90
references.pmid: 12657367
references.citation: Brain Res. 2004 Aug 20;1018(1):66-72
references.pmid: 15262206
references.citation: J Neurochem. 2002 Feb;80(3):438-47
references.pmid: 11908465
references.citation: Vision Res. 1998 May;38(10):1385-97
references.pmid: 9667006