Neuroprotective Effect of Lutein on NMDA-Induced Retinal Ganglion Cell Injury in Rat Retina

Cell Mol Neurobiol. 2016 May;36(4):531-40. doi: 10.1007/s10571-015-0231-5. Epub 2015 Jun 29.

Abstract

Lutein injection is 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 its protective effects in retinal ganglion cells (RGCs) against N-methyl-D-aspartate (NMDA)-induced retinal damage in vivo. Retinal damage was induced by intravitreal NMDA injection in rats. Each animal was given five daily intraperitoneal injections of Lutein or vehicle along with intravitreal NMDA injections. Electroretinograms were recorded. The number of viable RGCs was quantified using the retinal whole-mount method by immunofluorescence. Proteins were measured by Western blot assays. Lutein reduced the retinal damage and improved the response to light, as shown by an animal behavior assay (the black-and-white box method) in rats. Furthermore, Lutein treatment prevented the NMDA-induced reduction in phNR wave amplitude. Lutein increased RGC number after NMDA-induced retina damage. Most importantly, Bax, cytochrome c, p-p38 MAPK, and p-c-Jun were all upregulated in rats injected with NMDA, but these expression patterns were reversed by continuous Lutein uptake. Bcl-2, p-GSK-3β, and p-Akt in the Lutein-treated eyes were increased compared with the NMDA group. Lutein has neuroprotective effects against retinal damage, its protective effects may be partly mediated by its anti-excitability neurotoxicity, through MAPKs and PI3K/Akt signaling, suggesting a potential approach for suppressing retinal neural damage.

Keywords: Apoptosis; Lutein; MAPKs signaling; PI3K/Akt signaling; Retinal ganglion cell.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Behavior, Animal / drug effects
  • Blotting, Western
  • Caspase 3 / metabolism
  • Cell Count
  • Cytochromes c / metabolism
  • Electroretinography
  • Female
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Intravitreal Injections
  • Lutein / pharmacology*
  • Mitogen-Activated Protein Kinases / metabolism
  • N-Methylaspartate / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Photic Stimulation
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats, Sprague-Dawley
  • Retinal Ganglion Cells / drug effects*
  • Retinal Ganglion Cells / enzymology
  • Retinal Ganglion Cells / pathology
  • bcl-2-Associated X Protein / metabolism

Substances

  • Neuroprotective Agents
  • bcl-2-Associated X Protein
  • N-Methylaspartate
  • Cytochromes c
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases
  • Caspase 3
  • Lutein