GABAA 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 beta 1 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 beta 1 subunit in the death of retinal ganglion cells (RGCs) caused by oxidative stress. The retinal sites and expression pattern of GABA(A) receptor beta 1 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 beta 1 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. (c) 2008 Elsevier Ltd. All rights reserved.