title: Photoreceptor damage induced by low-intensity light: model of retinal degeneration in mammals.
abstract: OBJECTIVE
  Retinal degeneration caused by a defect in the phototransduction cascade leads to the apoptosis of photoreceptor cells, although the precise molecular mechanism is still unknown. In addition, constant low light exposure produces photoreceptor cell death through the activation of downstream phototransduction. The authors investigated the time course and molecular mechanisms of death and the rhodopsin phosphorylation occurring during retinal degeneration after exposure to continuous low-intensity light.
  
  
  METHODS
  Wistar rats were exposed to constant cool white 200 lx intensity LED light (LL) for one to ten days and compared with animals kept in the dark (DD) or controls exposed to a regular 12:12 h (LD) cycle. One eye from each rat was used for histological and quantitative outer nuclear layer (ONL) analysis and the other for biochemical assays.
  
  
  RESULTS
  The histological analysis showed a significant reduction in the ONL of LL-exposed rats after seven days compared with LD- or DD-exposed rats. Retinal analysis by flow cytometer and the TUNEL assay revealed an increase in cell death in the ONL, the in vitro enzymatic activity assay and western blot analysis showing no caspase-3 activation. The rhodopsin analysis demonstrated more phosphorylation in serine 334 residues (Ser(334)) in LL-exposed than in LD- or DD-exposed rats. However, for all times studied, rhodopsin was completely dephosphorylated after four days of DD treatment.
  
  
  CONCLUSIONS
  Constant light exposure for seven days produces ONL reduction by photoreceptor cell death through a capase-3-independent mechanism. Increases in rhodopsin-phospho-Ser(334) levels were observed, supporting the notion that changes in the regulation of the phototransduction cascade occur during retinal degeneration.
authors.affiliation: Centro de Investigaciones en Química Biológica, (CIQUIBIC, UNC-CONICET), Departamento de Química Biológica, Facultad de Ciencias Químicas,UNC, Haya de la Torre y Medina Allende, Ciudad Universitaria, X5000HUA, Córdoba, Argentina. mcontin@fcq.unc.edu.ar
authors.forename: Maria Ana
authors.initials: MA
authors.lastname: Contín
authors.forename: Milagros M
authors.initials: MM
authors.lastname: Arietti
authors.forename: María M
authors.initials: MM
authors.lastname: Benedetto
authors.forename: Claudio
authors.initials: C
authors.lastname: Bussi
authors.forename: Mario E
authors.initials: ME
authors.lastname: Guido
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000528:radiation effects; D004195:Disease Models, Animal; D020287:In Situ Nick-End Labeling; D008027:Light; D008322:Mammals / Q000378:metabolism*; D010766:Phosphorylation / Q000528:radiation effects; D010768:Phosphoserine / Q000378:metabolism; D020419:Photoreceptor Cells, Vertebrate / Q000201:enzymology / Q000473:pathology* / Q000528:radiation effects*; D011419:Propidium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012162:Retinal Degeneration / Q000201:enzymology / Q000473:pathology*; D012243:Rhodopsin / Q000378:metabolism
chemical_list: D017304:Annexin A5; D010768:Phosphoserine; D011419:Propidium; D012243:Rhodopsin; D053148:Caspase 3
references.citation: Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):974-8
references.pmid: 8302876
references.citation: Methods Enzymol. 2000;316:167-85
references.pmid: 10800675
references.citation: Curr Eye Res. 1991 Jan;10(1):47-59
references.pmid: 2029848
references.citation: Invest Ophthalmol Vis Sci. 1999 Nov;40(12):2978-82
references.pmid: 10549660
references.citation: Invest Ophthalmol Vis Sci. 2002 Mar;43(3):813-20
references.pmid: 11867603
references.citation: Neurosci Lett. 2004 Sep 2;367(2):205-9
references.pmid: 15331154
references.citation: Nat Med. 1995 Dec;1(12):1254-5
references.pmid: 7489404
references.citation: Biochem Cell Biol. 1994 Nov-Dec;72(11-12):499-503
references.pmid: 7654323
references.citation: Invest Ophthalmol Vis Sci. 2005 Aug;46(8):2671-82
references.pmid: 16043837
references.citation: Nat Rev Genet. 2010 Apr;11(4):273-84
references.pmid: 20212494
references.citation: Prog Retin Eye Res. 1998 Oct;17(4):443-64
references.pmid: 9777646
references.citation: Exp Eye Res. 2008 Mar;86(3):519-27
references.pmid: 18272151
references.citation: Invest Ophthalmol Vis Sci. 2011 Jul 07;52(8):5111-20
references.pmid: 21676907
references.citation: Photochem Photobiol. 1979 Apr;29(4):731-3
references.pmid: 451013
references.citation: Handb Exp Pharmacol. 2012;(208):79-94
references.pmid: 22222696
references.citation: Invest Ophthalmol Vis Sci. 2007 Jun;48(6):2753-9
references.pmid: 17525209
references.citation: Invest Ophthalmol Vis Sci. 2006 Dec;47(12):5204-11
references.pmid: 17122104
references.citation: Invest Ophthalmol Vis Sci. 1999 Nov;40(12):2770-2
references.pmid: 10549634
references.citation: Eye (Lond). 2011 Jan;25(1):1-14
references.pmid: 21178995
references.citation: Blood. 1994 Sep 1;84(5):1415-20
references.pmid: 8068938
references.citation: Proc Natl Acad Sci U S A. 1999 May 25;96(11):6072-7
references.pmid: 10339543
references.citation: Anal Biochem. 1976 May 7;72:248-54
references.pmid: 942051
references.citation: Biol Reprod. 1975 Dec;13(5):576-80
references.pmid: 1239315
references.citation: Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3551-5
references.pmid: 7724596
references.citation: Neuron. 2000 Oct;28(1):129-38
references.pmid: 11086989
references.citation: Invest Ophthalmol Vis Sci. 1983 Mar;24(3):285-7
references.pmid: 6832904
references.citation: Invest Ophthalmol Vis Sci. 2006 Jul;47(7):3109-18
references.pmid: 16799057
references.citation: Mol Vis. 2006 Aug 16;12:949-60
references.pmid: 16943767
references.citation: FEBS Lett. 1997 Aug 25;413(3):433-5
references.pmid: 9303550
references.citation: Ophthalmic Res. 1997;29(5):290-7
references.pmid: 9323720
references.citation: Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21695-700
references.pmid: 21098270
references.citation: J Biol Chem. 1995 Jun 16;270(24):14259-62
references.pmid: 7782279
references.citation: Prog Retin Eye Res. 2010 Mar;29(2):113-34
references.pmid: 19951742
references.citation: Curr Mol Med. 2009 Apr;9(3):375-83
references.pmid: 19355918
references.citation: Eur J Neurosci. 2003 Oct;18(7):1744-50
references.pmid: 14622209
references.citation: Neuroscience. 2005;130(2):397-407
references.pmid: 15664696
references.citation: Exp Eye Res. 1987 May;44(5):643-61
references.pmid: 3622645
references.citation: Am J Anat. 1971 Feb;130(2):227-33
references.pmid: 5547004
references.citation: J Biol Chem. 2001 Jun 22;276(25):23000-8
references.pmid: 11278285
references.citation: J Exp Med. 1995 Nov 1;182(5):1545-56
references.pmid: 7595224
references.citation: Curr Eye Res. 1996 Sep;15(9):914-22
references.pmid: 8921211
references.citation: Invest Ophthalmol Vis Sci. 2001 Oct;42(11):2589-95
references.pmid: 11581204
references.citation: Invest Ophthalmol Vis Sci. 2001 Mar;42(3):705-12
references.pmid: 11222531
references.citation: Arch Ophthalmol. 1968 Jan;79(1):69-78
references.pmid: 5635094
references.citation: Neuron. 1993 Oct;11(4):595-605
references.pmid: 8398150
references.citation: Clin Ophthalmol. 2008 Dec;2(4):821-8
references.pmid: 19668436
references.citation: Ophthalmologica. 1969;157(1):43-59
references.pmid: 5790890
references.citation: Arch Ophthalmol. 1996 Jan;114(1):79-83
references.pmid: 8540855
references.citation: Invest Ophthalmol Vis Sci. 2000 Nov;41(12):3984-90
references.pmid: 11053303
references.citation: Invest Ophthalmol Vis Sci. 2002 Oct;43(10):3349-54
references.pmid: 12356844
references.citation: Invest Ophthalmol Vis Sci. 1983 Jul;24(7):812-20
references.pmid: 6345445
references.citation: Neurochem Int. 2010 Oct;57(3):278-87
references.pmid: 20558223
references.citation: Trends Pharmacol Sci. 2004 Feb;25(2):105-11
references.pmid: 15102497
references.citation: Nat Genet. 2002 Oct;32(2):254-60
references.pmid: 12219089
references.citation: Cell Death Differ. 2002 Nov;9(11):1220-31
references.pmid: 12404121
references.citation: Photochem Photobiol. 2005 May-Jun;81(3):541-7
references.pmid: 15504085
references.citation: Neuron. 2001 Jul 19;31(1):87-101
references.pmid: 11498053
references.citation: Lab Anim Sci. 1987 Jun;37(3):289-98
references.pmid: 3613508
references.citation: Science. 1971 Apr 2;172(3978):72-5
references.pmid: 5546287
references.citation: Invest Ophthalmol. 1966 Oct;5(5):450-73
references.pmid: 5929286
references.citation: Am J Anat. 1973 Sep;138(1):127-32
references.pmid: 4741497
references.citation: Prog Retin Eye Res. 2005 Mar;24(2):275-306
references.pmid: 15610977
references.citation: Cell Tissue Res. 1986;246(3):607-21
references.pmid: 3791385