Dose-dependent prevention of sugar cataracts in galactose-fed dogs by the aldose reductase inhibitor M79175.
Sugar cataracts rapidly develop in dogs fed a diet containing 30% galactose. While studies on the formation and progression of these sugar cataracts suggest that they are osmotic in nature and are linked to aldose reductase, sugar cataract formation in the dog to date has not been completely prevented by the administration of aldose reductase inhibitors sorbinil and M79175. To demonstrate that the formation and progression of sugar cataracts in galactose-fed dogs can be dose-dependently inhibited by the administration of aldose reductase inhibitors, 9-month old male beagles were placed on diet containing 30% galactose with/without 10 or 16 mg kg-1 day-1 of M79175 for up to 39 months. Cataract progression in all dogs was followed by periodic slit lamp examination and documented by retroillumination photography. Although large variations in cataract formation and progression were observed, all dogs fed a 30% galactose diet for 39 months developed cataracts. Lens changes were significantly less in galactose-fed dogs treated with either 10 or 16 mg kg-1 M79175 and no cataract formation was observed in 3 of 6 galactose-fed dogs treated with 16 mg kg-1 M79175. These observations confirm that aldose reductase plays a key role in initiating cataract formation in galactose-fed dogs and that cataract formation can be prevented by adequate inhibition of aldose reductase.
Sato
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S
Laboratory of Ocular Therapeutics, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-1850, USA.
Mori
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K
Wyman
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M
Kador
P F
PF
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D002386:Cataract / Q000139:chemically induced*; D004040:Dietary Carbohydrates / Q000633:toxicity; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005690:Galactose / Q000008:administration & dosage / Q000633:toxicity*; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D008297:Male
D004040:Dietary Carbohydrates; D004791:Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; C037070:M 79175; D000449:Aldehyde Reductase; D005690:Galactose