Regulation of glutamate transporter in rat retina under ischemia-reperfusion

Glutamate is the major excitatory neurotransmitter in the mammalian retina where excessive accumulation has been implicated in the pathogenesis of glaucoma. In a rat model of glaucoma induced by transient elevation of intraocular pressure (IOP), increase of extracellular glutamate causes delayed ganglion cell loss, offering a useful model to study glaucoma. It is well known that glutamate transport is a crucial mechanism for maintaining glutamate homeostasis under normal and pathological conditions. Thus, in the attempt to better understand the role of glutamate regulation system in the pathogenesis of glaucoma, we examined the changes in glial glutamate transporter 1 (GLT-1) expression and activity by immunohistochemistry and synaptosomal preparation from the retina of rats subjected to high IOP-induced ischemia. Our results indicate that GLT1 expression was significantly increased in the ischemic retina. In contrast, GLT-1 activity decreased during the same experimental period. Particularly, synaptosome’s uptake was reduced by 30% and neurotransmitter release, operated by transporter reversal, showed a similar decrease in ischemic tissue. These data suggest that GLT-1 may be a prerequisite for the maintenance of glutamate homeostasis in the retina subjected to high IOP.