GABA A receptors are associated with retinal ganglion cell death induced by oxidative stress

Exp Eye Res. 2008 May;86(5):727-33. doi: 10.1016/j.exer.2008.01.019. Epub 2008 Feb 3.


A previously proteomic study from our laboratory showed that the expression of the protein of the GABA A receptor beta1 subunit was significantly increased in the retina of EAAC1-deficient (EAAC1-/-) mice, a mouse model of glaucoma. The purpose of this study was to investigate the role played by GABA A receptor beta1 subunit in the death of retinal ganglion cells (RGCs) caused by oxidative stress. The retinal sites and expression pattern of GABA A receptor beta1 subunit were determined by immunohistochemistry in the retina of ICR mice. A RGC line, RGC-5, was exposed to GABA A receptor agonist and antagonist, and the cell viability was determined by the MTS assay. The effect of GABA A receptor antagonist on the death of RGCs, and the activation of oxidative stress signaling induced by hydrogen peroxide was investigated. Our results showed that the GABA A receptor beta1 subunit was expressed on the RGCs of ICR mice. GABA A receptor agonist induced RGCs death, and this death was inhibited by bicuculline, a GABA A receptor antagonist. The hydrogen peroxide-induced death of RGCs was reduced by GABA A receptor antagonist, and the oxidative stress signaling activated by hydrogen peroxide was also inhibited. These results indicate that GABA A receptors are expressed on RGCs and may play a role in the death of RGCs induced by oxidative stress.

MeSH terms

  • Animals
  • Bicuculline / pharmacology
  • Blotting, Western
  • Cell Death / drug effects
  • Cell Death / physiology
  • Cell Line
  • GABA Agonists / pharmacology
  • GABA Antagonists / pharmacology
  • GABA-A Receptor Agonists
  • GABA-A Receptor Antagonists
  • Hydrogen Peroxide / pharmacology
  • Mice
  • Mice, Inbred ICR
  • Muscimol / pharmacology
  • Neuroprotective Agents / pharmacology
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology*
  • Rats
  • Receptors, GABA-A / metabolism
  • Receptors, GABA-A / physiology*
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / metabolism
  • Retinal Ganglion Cells / pathology*
  • Signal Transduction / physiology
  • Transfection
  • Up-Regulation


  • GABA Agonists
  • GABA Antagonists
  • GABA-A Receptor Agonists
  • GABA-A Receptor Antagonists
  • Neuroprotective Agents
  • Receptors, GABA-A
  • Muscimol
  • Hydrogen Peroxide
  • Bicuculline