Anti-inflammatory effects of lutein in retinal ischemic/hypoxic injury: in vivo and in vitro studies

Invest Ophthalmol Vis Sci. 2012 Sep 6;53(10):5976-84. doi: 10.1167/iovs.12-10007.


Purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Blotting, Western
  • Cells, Cultured
  • Cobalt / toxicity
  • Cyclooxygenase 2 / metabolism
  • Disease Models, Animal
  • Electroretinography
  • Glial Fibrillary Acidic Protein
  • Hypoxia / metabolism
  • Hypoxia / prevention & control*
  • Interleukin-1beta / metabolism
  • Lutein / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Nerve Tissue Proteins / metabolism
  • Neuroglia / drug effects*
  • Neuroglia / metabolism
  • Photic Stimulation
  • Rats
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control*
  • Retina / physiopathology
  • Retinal Diseases / metabolism
  • Retinal Diseases / physiopathology
  • Retinal Diseases / prevention & control*
  • Tumor Necrosis Factor-alpha / metabolism


  • Anti-Inflammatory Agents, Non-Steroidal
  • Glial Fibrillary Acidic Protein
  • Interleukin-1beta
  • NF-kappa B
  • Nerve Tissue Proteins
  • Tumor Necrosis Factor-alpha
  • glial fibrillary astrocytic protein, mouse
  • Cobalt
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • cobaltous chloride
  • Lutein