A physiological level of ascorbate inhibits galactose cataract in guinea pigs by decreasing polyol accumulation in the lens epithelium: a dehydroascorbate-linked mechanism.
It was reported previously that dietary ascorbate (ASC) delays the development of galactose-induced cataract in guinea pigs compared to the rate which is observed in ASC-deficient animals. Experiments were conducted to explore the possible mechanism of this phenomenon. Guinea pigs were fed for a period of up to 4 weeks either a normal diet (1 g ASC/kg diet) or a scorbutic diet (< 0.04 g ASC/kg diet) combined with 10% galactose in the drinking water. After 2 weeks, levels of ASC in animals on the scorbutic diet decreased by 95% in the aqueous humor and by 78% in the lens. Slit lamp examination showed that galactose-induced vacuoles in the lens equator formed at a significantly faster rate in the scorbutic animals. However, examination of biochemical parameters in whole lenses of the two groups of animals after 2 weeks showed no significant differences with regard to accumulation of galactose and galactitol, decreases in the levels of myoinositol, taurine and GSH or changes in cation concentrations. In order to examine possible regional changes in the lenses, various parameters were studied in the lens capsule-epithelium. On day 4, the capsule epithelia of scorbutic animals on a galactose diet had a content of galactitol two-and-a-half times higher than that of normal galactose-fed animals. Scorbutic conditions also intensified the loss of Na(+)-K+ ATPase activity in the lens capsule-epithelium caused by galactose feeding. Oxidized glutathione was not detectable in the lens capsule epithelia of any of the animals studied. Hexose monophosphate shunt activity was elevated in lenses of normal galactose-fed animals during the first hour of culture after death whereas lenses of scorbutic galactose-fed animals were not. Consistent with the in vivo findings, galactitol accumulation in dog lens epithelial cells exposed to 30 mM galactose was significantly inhibited by the presence of either ASC or dehydroascorbate (DHA) in the medium. Hexose monophosphate shunt activity in the cells was stimulated to two-and-a-half times its initial level by either 1 mM DHA or 30 mM galactose and slightly more than three-fold by a combination of the two challenges. The results suggest that decreased polyol accumulation in the lens epithelium of the normal galactose-fed guinea pig, which has a high level of ASC in the aqueous humor, accounts for the delay in onset of cataract compared to that for the ASC-deficient animal.(ABSTRACT TRUNCATED AT 400 WORDS)
Yokoyama
T
T
Eye Research Institute, Oakland University, Rochester, MI 48309-4401.
Sasaki
H
H
Giblin
F J
FJ
Reddy
V N
VN
D000818:Animals; D001082:Aqueous Humor / Q000737:chemistry; D001205:Ascorbic Acid / Q000627:therapeutic use*; D002386:Cataract / Q000139:chemically induced / Q000517:prevention & control*; D002478:Cells, Cultured; D003683:Dehydroascorbic Acid / Q000494:pharmacology; D004285:Dogs; D005260:Female; D004376:Galactitol / Q000032:analysis; D005690:Galactose; D005978:Glutathione / Q000032:analysis; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000032:analysis; D007294:Inositol / Q000032:analysis; D007908:Lens, Crystalline / Q000737:chemistry / Q000187:drug effects; D009249:NADP / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D004376:Galactitol; D007294:Inositol; D009249:NADP; D006861:Hydrogen Peroxide; D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione; D001205:Ascorbic Acid; D005690:Galactose; D003683:Dehydroascorbic Acid