PCMPS-INDUCED CHANGES IN LENS MEMBRANE-PERMEABILITY AND TRANSPARENCY

Purpose. To investigate the role of externally facing membrane protein sulfhydryl groups in controlling lens permeability and transparency using the impermeant sulfhydryl complexing agent p-chloromercuriphenyl sulfonate (pCMPS). Methods. Membrane permeability changes were studied by measuring lens voltage and resistance. Ion movements were monitored by measuring Na-22+ and Ca-45(2+) fluxes, and internal free calcium was monitored by ion-selective microelectrodes. Opacification was quantified by photographing and analyzing back-scattered light. Results. pCMPS, at concentrations above 1 muM, produced a depolarization of membrane potential and decrease in membrane resistance. These changes were accompanied by a marked stimulation in Na-22+ and Ca-45(2+) influxes into the lens. There was a concomitant loss of lens transparency, mainly in the bow region. The pCMPS-induced electrical changes could be prevented by substituting N-methyl-D-glucamine for Na+ in the external medium. Na+-free solution alone increased Ca-45(2+) influx, and the addition of pCMPS further stimulated the influx. Quinine (300 muM) was found to reduce the pCMPS-induced stimulation of Na-22+ and Ca-45(2+) influxes and also to reduce opacification. Conclusions. pCMPS at low concentrations induces many of the cation permeability changes previously found to occur with age and cataract in the lens. The fact that quinine can ameliorate pCMPS-induced changes in ion movements and opacification suggests a novel approach for membrane-based anticataract strategies.