title: Neuroprotective effect of an antioxidant, lutein, during retinal inflammation.
abstract: OBJECTIVE
  Lutein has been the focus of recent study as a possible therapeutic approach for retinal diseases, but the molecular mechanism of its neuroprotective effect remains to be elucidated. The aim of this study was to investigate, with the use of a mouse endotoxin-induced uveitis (EIU) model, the neuroprotective effects of lutein against retinal neural damage caused by inflammation.
  
  
  METHODS
  EIU was induced by intraperitoneal injection of lipopolysaccharide (LPS). Each animal was given a subcutaneous injection of lutein or vehicle three times: concurrently with and 3 hours before and after the LPS injection. Analysis was carried out 24 hours after EIU induction. Levels of rhodopsin protein and STAT3 activation were analyzed by immunoblotting. Lengths of the outer segments of the photoreceptor cells were measured. Dark-adapted full-field electroretinograms were recorded. Oxidative stress in the retina was analyzed by dihydroethidium and fluorescent probe. Expression of glial fibrillary acidic protein (GFAP) was shown immunohistochemically.
  
  
  RESULTS
  The EIU-induced decrease in rhodopsin expression followed by shortening of the outer segments and reduction in a-wave amplitude were prevented by lutein treatment. Levels of STAT3 activation, downstream of inflammatory cytokine signals, and reactive oxygen species (ROS), which are both upregulated during EIU, were reduced by lutein. Pathologic change of Müller glial cells, represented by GFAP expression, was also prevented by lutein.
  
  
  CONCLUSIONS
  The present data revealed that the antioxidant lutein was neuroprotective during EIU, suggesting a potential approach for suppressing retinal neural damage during inflammation.
authors.affiliation: Department of Ophthalmology, Laboratory of Retinal Cell Biology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Sasaki
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ozawa
authors.forename: Toshihide
authors.initials: T
authors.lastname: Kurihara
authors.forename: Kousuke
authors.initials: K
authors.lastname: Noda
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Imamura
authors.forename: Saori
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Susumu
authors.initials: S
authors.lastname: Ishida
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsubota
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004596:Electroretinography; D004926:Escherichia coli; D005904:Glial Fibrillary Acidic Protein; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D008070:Lipopolysaccharides; D014975:Lutein / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012173:Retinitis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012243:Rhodopsin / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015866:Uveitis, Posterior / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D000975:Antioxidants; D005904:Glial Fibrillary Acidic Protein; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C528900:glial fibrillary astrocytic protein, mouse; D012243:Rhodopsin; D014975:Lutein