title: Anti-inflammatory effects of lutein in retinal ischemic/hypoxic injury: in vivo and in vitro studies.
abstract: OBJECTIVE
  Lutein protects retinal neurons by its anti-oxidative and anti-apoptotic properties in ischemia/reperfusion (I/R) injury while its anti-inflammatory effects remain unknown. As Müller cells play a critical role in retinal inflammation, the effect of lutein on Müller cells was investigated in a murine model of I/R injury and a culture model of hypoxic damage.
  
  
  METHODS
  Unilateral retinal I/R was induced by a blockade of internal carotid artery using the intraluminal method in mice. Ischemia was maintained for 2 hours followed by 22 hours of reperfusion, during which either lutein (0.2 mg/kg) or vehicle was administered. Flash electroretinogram (flash ERG) and glial fibrillary acidic protein (GFAP) activation were assessed. Lutein's effect on Müller cells was further evaluated in immortalized rat Müller cells (rMC-1) challenged with cobalt chloride-induced hypoxia. Levels of IL-1β, cyclooxygenase-2 (Cox-2), TNFα, and nuclear factor-NF-kappa-B (NF-κB) were examined by Western blot analysis.
  
  
  RESULTS
  Lutein treatment minimized deterioration of b-wave/a-wave ratio and oscillatory potentials as well as inhibited up-regulation of GFAP in retinal I/R injury. In cultured Müller cells, lutein treatment increased cell viability and reduced level of nuclear NF-κB, IL-1β, and Cox-2, but not TNFα after hypoxic injury.
  
  
  CONCLUSIONS
  Reduced gliosis in I/R retina was observed with lutein treatment, which may contribute to preserved retinal function. Less production of pro-inflammatory factors from Müller cells suggested an anti-inflammatory role of lutein in retinal ischemic/hypoxic injury. Together with our previous studies, our results suggest that lutein protected the retina from ischemic/hypoxic damage by its anti-oxidative, anti-apoptotic, and anti-inflammatory properties.
authors.affiliation: Eye Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People’s Republic of China.
authors.forename: Suk-Yee
authors.initials: SY
authors.lastname: Li
authors.forename: Frederic K C
authors.initials: FK
authors.lastname: Fung
authors.forename: Zhong Jie
authors.initials: ZJ
authors.lastname: Fu
authors.forename: David
authors.initials: D
authors.lastname: Wong
authors.forename: Henry H L
authors.initials: HH
authors.lastname: Chan
authors.forename: Amy C Y
authors.initials: AC
authors.lastname: Lo
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D003035:Cobalt / Q000633:toxicity; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D004596:Electroretinography; D005904:Glial Fibrillary Acidic Protein; D000860:Hypoxia / Q000378:metabolism / Q000517:prevention & control*; D053583:Interleukin-1beta / Q000378:metabolism; D014975:Lutein / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D010775:Photic Stimulation; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D012160:Retina / Q000503:physiopathology; D012164:Retinal Diseases / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005904:Glial Fibrillary Acidic Protein; D053583:Interleukin-1beta; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D014409:Tumor Necrosis Factor-alpha; C528900:glial fibrillary astrocytic protein, mouse; D003035:Cobalt; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C018021:cobaltous chloride; D014975:Lutein