Identification, Expression, and Roles of the Cystine/Glutamate Antiporter in Ocular Tissues.

Abstract

The cystine/glutamate antiporter (system <i>x</i> _c ^-) is composed of a heavy chain subunit 4F2hc linked by a disulphide bond to a light chain xCT, which exchanges extracellular cystine, the disulphide form of the amino acid cysteine, for intracellular glutamate. <i>In vitro</i> research in the brain, kidney, and liver have shown this antiporter to play a role in minimising oxidative stress by providing a source of intracellular cysteine for the synthesis of the antioxidant glutathione. <i>In vivo</i> studies using the xCT knockout mouse revealed that the plasma cystine/cysteine redox couple was tilted to a more oxidative state demonstrating system x_c ^- to also play a role in maintaining extracellular redox balance by driving a cystine/cysteine redox cycle. In addition, through import of cystine, system x_c ^- also serves to export glutamate into the extracellular space which may influence neurotransmission and glutamate signalling in neural tissues. While changes to system x_c ^- function has been linked to cancer and neurodegenerative disease, there is limited research on the roles of system x_c ^- in the different tissues of the eye, and links between the antiporter, aging, and ocular disease. Hence, this review seeks to consolidate research on system x_c ^- in the cornea, lens, retina, and ocular humours conducted across several species to shed light on the <i>in vitro</i> and <i>in vivo</i> roles of xCT in the eye and highlight the utility of the xCT knockout mouse as a tool to investigate the contribution of xCT to age-related ocular diseases.