Involvement of aldose reductase in naphthalene cataract.
OBJECTIVE
The authors investigated the involvement of the enzyme aldose reductase (AR) in naphthalene cataract by using transgenic mice that overexpress AR.


METHODS
Lenses from nontransgenic mice and from transgenic lines CAR222 and CAR648, with different levels of AR, were cultured in medium containing naphthalene-1,2-dihydrodiol (ND) with or without AR inhibitor AL1576. The morphology and progression rate of ND-induced cataract in these lenses were compared.


RESULTS
Lenses from transgenic mice CAR222 and CAR648, but not their nontransgenic littermates, developed yellow pigment in the inner cortex when exposed to 50 microM ND, which was completely prevented by 0.2 mM AL1576. The yellow pigment developed faster and more intensely in the CAR648 lens, which has a higher AR level than CAR222. Under a high dose of 500 microM ND, both transgenic and wild-type mouse lenses developed ND-induced cataract, although the first sign of cataract was found in the outer cortex in transgenic lenses instead of the inner cortical region in wild-type lenses. In addition, the cataract was more severe and developed at a faster rate in transgenic mouse lenses. AL1576 showed only partial protection against the cataract induced by 500 microM ND.


CONCLUSIONS
The findings showed that the progression rate of ND-induced cataract correlated with the level of lens AR and ND, indicating that AR was the key enzyme for the metabolism of ND in the process of naphthalene cataract development.
Lee
A Y
AY
Institute of Molecular Biology, University of Hong Kong, Pokfulam.
Chung
S S
SS
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002386:Cataract / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D003470:Culture Media; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005449:Fluorenes / Q000494:pharmacology; D006827:Hydantoins / Q000494:pharmacology; D007908:Lens, Crystalline / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009284:Naphthols / Q000633:toxicity*; D009924:Organ Culture Techniques
D003470:Culture Media; D004791:Enzyme Inhibitors; D005449:Fluorenes; D006827:Hydantoins; D009284:Naphthols; C052241:imirestat; C042334:1,2-dihydroxy-1,2-dihydronaphthalene; D000449:Aldehyde Reductase