Polyol accumulation in cultured human lens epithelial cells.
Human lens epithelial (HLE) cells in tissue culture accumulated significant levels of galactitol when they were cultured for 72 hr in medium containing 30 mM D-galactose. Polyol accumulation was accompanied by the appearance of vacuoles as seen by transmission electron microscopy. The number and size of intracellular vacuoles increased when the culture period was extended to 7 days. In addition, polyol accumulation was accompanied by loss of myoinositol. None of these changes occurred in cells exposed to 30 M L-galactose which is not a substrate for aldose reductase. The accumulation of galactitol, intracellular vacuole formation and loss of myoinositol observed in D-galactose-exposed cells were prevented by the inclusion of the aldose reductase inhibitor, sorbinil, in the culture medium. Comparison of the relative efficacies of two aldose reductase inhibitors indicate that AL 1576 is nearly 20 times more potent than sorbinil in inhibiting the human lens enzyme. It is concluded that vacuole formation in HLE cells is due to the osmotic effect of polyol formation brought about by the action of aldose reductase and that the etiology of human diabetic cataract may also involve the polyol pathway.
Lin
L R
LR
Eye Research Institute, Oakland University, Rochester, MI 48309-4401.
Reddy
V N
VN
Giblin
F J
FJ
Kador
P F
PF
Kinoshita
J H
JH
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism; D002478:Cells, Cultured; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism / Q000648:ultrastructure; D005449:Fluorenes / Q000494:pharmacology; D004376:Galactitol / Q000096:biosynthesis; D005690:Galactose / Q000494:pharmacology; D006801:Humans; D006827:Hydantoins / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D007294:Inositol / Q000378:metabolism; D007908:Lens, Crystalline / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008858:Microscopy, Phase-Contrast; D011108:Polymers / Q000378:metabolism*; D012016:Reference Values; D013237:Stereoisomerism; D014617:Vacuoles / Q000378:metabolism / Q000648:ultrastructure
D005449:Fluorenes; D006827:Hydantoins; D007093:Imidazoles; D048289:Imidazolidines; D011108:Polymers; C024617:polyol; C052241:imirestat; D004376:Galactitol; D007294:Inositol; D000449:Aldehyde Reductase; C026411:sorbinil; D005690:Galactose