Establishment of a naphthalene cataract model in vitro.
In the past, almost all studies on naphthalene cataract were based on in vivo experiments. Such studies are laborious and time-consuming and are complicated by systemic toxicity arising from the metabolites of naphthalene. In order to study the direct effects of naphthalene metabolites on the lens, we established an in vitro 'naphthalene cataract' model system by exposing rat lens to naphthalene dihydrodiol (2.5 x 10(5) M) containing medium for 48 hr. Under these conditions, we analysed several biochemical parameters including the glutathione level, protein mixed disulfides, protein patterns on SDS-gels, active transport, NA+/K(+)-ATPase activities and the measurement of naphthalene metabolites in the cultured lenses. The results showed that both the morphological and biochemical changes were very similar to those observed in lenses of rats fed naphthalene (1 g kg-1 day-1). Furthermore, ALO1576 completely blocked the in vitro changes as it did in vivo. Therefore, this model system can be used as a new tool to investigate the mechanism of naphthalene cataract formation. Other naphthalene metabolites such as 1-naphthol, 2-naphthol, 1,2-dihydroxynaphthalene and 1,2-naphthoquinone were also studied in vitro and the results showed that the effects of these naphthalene metabolites were very different from those observed in naphthalene cataracts in vivo.
Xu
G T
GT
Cataract Research, Alcon Laboratories Inc., Fort Worth, TX 76115.
Zigler
J S
JS
Lou
M F
MF
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000818:Animals; D002386:Cataract / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D046508:Culture Techniques; D005449:Fluorenes / Q000494:pharmacology; D006827:Hydantoins / Q000494:pharmacology; D007908:Lens, Crystalline / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008954:Models, Biological; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D005449:Fluorenes; D006827:Hydantoins; D009281:Naphthalenes; C052241:imirestat; D000449:Aldehyde Reductase