Lens GSH depletion and electrolyte changes preceding cataracts induced by buthionine sulfoximine in suckling mice

Abstract

Cataracts were induced in suckling mice by multiple injections of l-buthionine-S,R-sulfoximine (BSO), a specific inhibitor of GSH biosynthesis, starting on post-natal day 7. The earliest visible lens aberrations began approximately 2 days after t 0, following 99% depletion of lens GSH. Cataract development then proceeded through four stages within less than 24 hr. Elevated Na + and Ca + and decreased K + were first detected in pre-cataractous (stage 0) lenses. During stage 0, lens Na + and K + levels displayed a significant inverse correlation; by contrast, Ca 2+ levels were poorly correlated with those of Na +. The initial increase in Na + exceeded the decrease in K +. This suggested the presence of osmotic stress prior to cataract stage 1 (developing floriform). Increased lens hydration was first apparent in stage 1, coincident with a marked elevation of Ca 2+, further increase in Na + and decrease in K +. These trends persisted in the stage 2 cataract (completed floriform). Subsequent changes in lens hydration and cation content during cataract stages 3 (degenerate floriform) and 4 (amorphous translucent) suggested substantial influx of extracellular fluid into the affected lenses. The BSO cataract may represent a useful in vivo model to study the functions of GSH in maintaining normal lens cation balance and transparency.