An impediment to glutathione diffusion in older normal human lenses: a possible precondition for nuclear cataract

Human age-related nuclear cataract is associated with progressive and wides pread oxidation of proteins, particularly in the centre of the lens. The re asons for the onset of cataract and why this disease should take place only in the lenses of older individuals remain unclear. However, a common featu re of nuclear cataract is the low concentration of reduced glutathione (GSH ) in the centre of the lens. GSH is the principal lenticular antioxidant of the lens and it is synthesized and regenerated in the lens cortex. In this study we investigated the diffusion of glutathione within the human lens a s a function of age. Normal human lenses were incubated in artificial aqueo us humor containing [S-35]cysteine and the label was metabolically incorpor ated into GSH. After 48-h incubation, lenses were sectioned and phosphorima ging was used to determine the distribution of 35S label. In young lenses, label appeared to diffuse uniformly throughout the whole lens. By contrast, in lenses over the age of 30, very little S-35 had penetrated to the centr e of the lens. A distinct zonal pattern of label distribution was noted in the older lenses after 48 h incubation, which had dimensions of approximate ly 7.2 mm (diameter) by 2.8 mm (axial). In some older lenses this pattern w as noticeable even after 96-h incubation. Thus a barrier to the diffusion o f GSH was observed in older normal lenses which was not present in younger lenses. Furthermore, the internal zone thus delineated has dimensions that coincide with those of the coloured and sclerotic zone present in nuclear c ataract lenses. Since nuclear cataract is a disease of the elderly, and mai ntenance of GSH is known to be vital for lens clarity, we propose that the development of a barrier to the movement of GSH from its site of synthesis and regeneration in the cortex, into the nucleus in older normal lenses, ma y over time allow oxidative modification of protein to take place in the nu cleus, resulting ultimately in nuclear cataract. (C) 1998 Academic Press.