Copper exchanges and toxicity in the rabbit lens in vitro.

Lenses (in vitro) exposed to 10(-4) M Cu for 24 hr gained an excess of Na and lost K. Incubation for 7 days with 10(-5) M Cu had a similar toxic effect. Threonine, which is present in aqueous humor, increased sensitivity of lenses to Cu, and also uptake of 64Cu. Uptake of 64Cu commenced reaching tissue saturation levels in 5 hr at 10(-7) M Cu. At higher concentrations, uptake was greater (1263 X for a 1000-fold rise in concentration from 10(-7) -10(-4) M) and saturation was not seen in this time. Autoradiography of sections of such lenses suggested that accumulation of the 64Cu occurred principally within the region of the cells of the anterior epithelium and capsule and lens bow. Efflux of accumulated 64Cu occurred more rapidly when copper was present in the external media suggesting the presence of 'specific' binding sites for copper. Percentage retention of accumulated 64Cu was greater in lenses loaded in 10(-6) M than 10(-5) M Cu. It is suggested that copper can enter lenses, possibly facilitated by threonine, and can bind to two types of sites: one with a high affinity but low capacity for the metal ion, the other with a lower affinity but larger capacity. The former may be concerned with the physiological roles and normal metabolism of copper and the latter with its toxic actions.