The importance of membrane sulfhydryl groups to calcium homeostasis in the lens

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Abstract
This study focused on whether changes in lens levels of glutathione [GSH] and Ca, early events associated with cataract formation, were related or that one might cause the other. The first part of the investigation was concerned with the extent to which an increase in levels of intracellular Ca might alter GSH levels in lens fiber and epithelial cells. The results demonstrate that Ca accumulation, either at 19.degree. C or 37.degree. C, did not diminish the concentration of GSH. More importantly, GSH levels did not decline in opaque regions of a Ca-loaded lens. The reciprocal part of the problem focused on whether a decline in lens thiol might lead to an increase in levels of Ca and subsequent opacification. In particular, it was shown that treatment of lenses with parachloromercuribenzene sulphonic acid (PCMBS), a nonpenetrating sulphhydryl probe, resulted in a 10-30% loss of membrane SH groups in the epithelium. Diminished numbers of SH groups was accompanied by chloride fluxes and an increase in membrane permeability to Na and Ca with an influx of Na and Ca leading to opacities. It is important to note that these changes occurred in the absence of any change in cellular levels of soluble protein-SH or GSH. Additional experiments suggest that Ca transport was not impaired, as evidenced by lack of inhibition of Ca-ATPase activity in lenses treated with PCMBS. The results suggest that one explanation for opacification is that oxidative insults, which diminish GSH levels, leads to a loss of important membrane SH groups. An increase in membrane permeability to Ca and other ions quickly follows the loss of thiol followed by an accumulation of lens Ca and subsequent opacification.

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