GABA A receptors are associated with retinal ganglion cell death induced by oxidative stress.
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.
Okumichi
Hideaki
H
Department of Ophthalmology and Visual Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3, Kasumi, Hiroshima 734-8551, Japan.
Mizukami
Mina
M
Kiuchi
Yoshiaki
Y
Kanamoto
Takashi
T
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009118:Muscimol / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D015854:Up-Regulation
D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D018696:Neuroprotective Agents; D011963:Receptors, GABA-A; D009118:Muscimol; D006861:Hydrogen Peroxide; D001640:Bicuculline