Distribution of ascorbic acid and GSH transporters in the anterior eye. All tissues appear to express similar transport mechanisms for accumulating ascorbic acid (AA) or DHA and GSH. (a) In the corneal epithelium, AA is directly accumulated from the tear fluid by SVCT2, while in the corneal endothelium, the oxidised form of AA, DHA, is taken up from the aqueous via GLUT1. In the corneal epithelium, transport of GSH precursor amino acids such as glutamate (EAATs) and cystine () have been identified as well as GSH efflux transporters such as MRP4/5. On the other hand, GSH uptake transporters OAT3 and NaDC3 were identified in the corneal endothelium, indicating that the different layers of the cornea contain different transport mechanisms for maintaining GSH levels. (b) In the lens, uptake of AA may be mediated by SVCT2 in the epithelium and AQP0 in cortical fibre cells while uptake of DHA is likely to be mediated by GLUT1 in the epithelium and GLUT3 in cortical fibre cells. GSH precursor amino acids for glutamate (EAATs), cystine (), and glycine (GLYT1/2) have been identified in the outer cortex of the lens. Interestingly, , GLYT2, and ASCT2 which transport glutamate at low pH, which coincide with the acidic environment of the nucleus, were also found in the lens nucleus. Since protein synthesis does not occur in this region of the lens, it has been proposed that cystine may be accumulated and then reduced to cysteine in the lens core where it can act directly as a low molecular mass antioxidant. GSH uptake transporters (OAT3) appear to be localised predominantly to the lens epithelium. (c) In the ciliary body, SVCT2 was localised to the PE layer indicating that AA in the ciliary body is taken up from the stroma. GSH precursor amino acid transporters for cystine () and glycine (GLYT2) have been identified in the NPE layer suggesting that these amino acids can be directly accumulated from the aqueous. Similarly GSH uptake transporters (OAT3) have been identified in the NPE layer. GSH efflux transporters (MRP1/4/5) have also been identified in the PE and NPE cell layers and may be involved in the removal of GSH conjugates either into the stroma or possibly into the aqueous and then removed via the trabecular meshwork. (d) To date, identification of AA and GSH uptake transporters in the trabecular meshwork is unknown.
