Lens GSH depletion and electrolyte changes preceding cataracts induced by buthionine sulfoximine in suckling mice.
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(o), 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, Ca2+ 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 Ca2+, 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.
Calvin
H I
HI
Department of Ophthalmology, Biochemistry and Molecular Biology, UMD-NJ Medical School, Newark 07103.
von Hagen
S
S
Hess
J L
JL
Patel
S A
SA
Fu
S C
SC
D000818:Animals; D019328:Buthionine Sulfoximine; D002118:Calcium / Q000378:metabolism; D002386:Cataract / Q000139:chemically induced / Q000378:metabolism*; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D007908:Lens, Crystalline / Q000378:metabolism*; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives; D051379:Mice; D008815:Mice, Inbred Strains; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013997:Time Factors
D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D012964:Sodium; D005978:Glutathione; D011188:Potassium; D002118:Calcium