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Effects of topical administration of an aldose reductase inhibitor on cataract formation in dogs fed a diet high in galactose

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  • 1 College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198
  • | 2 Therapeutic Vision Inc, 11778 Whitmore S, Omaha, NE 68142
  • | 3 Therapeutic Vision Inc, 11778 Whitmore S, Omaha, NE 68142
  • | 4 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011
  • | 5 Therapeutic Vision Inc, 11778 Whitmore S, Omaha, NE 68142
  • | 6 Department of Comparative Ophthalmology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210
  • | 7 College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198
  • | 8 College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198

Abstract

Objective—To determine effects of a topical formulation of an aldose reductase inhibitor (ARI) on the development of sugar cataracts in dogs fed a diet high in galactose.

Animals—Ten 6-month old Beagles.

Procedures—Dogs were fed a diet containing 30% galactose, and after 16 weeks, 6 dogs were treated topically with a proprietary ARI formulation and 4 dogs were treated with a placebo. Cataract formation was monitored by means of slit-lamp biomicroscopy and fundus photography. Dogs were euthanized after 10 weeks of treatment, and lenses were evaluated for degree of opacity, myo-inositol and galactitol concentrations, and concentration of the ARI.

Results—All dogs developed bilateral cortical opacities dense enough to result in a decrease in the tapetal reflex after being fed the galactose-containing diet for 16 weeks. Administration of the ARI arrested further development of cataract formation. In contrast, cataracts in the vehicle-treated dogs progressed over the 10-week period to the mature stage. Evaluation of the isolated lenses after 26 weeks of galactose feeding indicated that lenses from treated dogs were significantly less optically dense than lenses from control dogs. Lenticular myo-inositol concentration was significantly higher in the treated than in the control dogs.

Conclusions and Clinical Relevance—Results suggest that topical application of a proprietary ARI formulation may arrest or reverse the development of sugar cataracts in dogs fed a diet high in galactose. This suggests that this ARI formulation may be beneficial in maintaining or improving functional vision in diabetic dogs with early lens opacities.

Abstract

Objective—To determine effects of a topical formulation of an aldose reductase inhibitor (ARI) on the development of sugar cataracts in dogs fed a diet high in galactose.

Animals—Ten 6-month old Beagles.

Procedures—Dogs were fed a diet containing 30% galactose, and after 16 weeks, 6 dogs were treated topically with a proprietary ARI formulation and 4 dogs were treated with a placebo. Cataract formation was monitored by means of slit-lamp biomicroscopy and fundus photography. Dogs were euthanized after 10 weeks of treatment, and lenses were evaluated for degree of opacity, myo-inositol and galactitol concentrations, and concentration of the ARI.

Results—All dogs developed bilateral cortical opacities dense enough to result in a decrease in the tapetal reflex after being fed the galactose-containing diet for 16 weeks. Administration of the ARI arrested further development of cataract formation. In contrast, cataracts in the vehicle-treated dogs progressed over the 10-week period to the mature stage. Evaluation of the isolated lenses after 26 weeks of galactose feeding indicated that lenses from treated dogs were significantly less optically dense than lenses from control dogs. Lenticular myo-inositol concentration was significantly higher in the treated than in the control dogs.

Conclusions and Clinical Relevance—Results suggest that topical application of a proprietary ARI formulation may arrest or reverse the development of sugar cataracts in dogs fed a diet high in galactose. This suggests that this ARI formulation may be beneficial in maintaining or improving functional vision in diabetic dogs with early lens opacities.

Contributor Notes

Supported by start-up funds provided by the University of Nebraska Medical Center.

Drs. Kador, Betts, and Wyman have financial interests in Therapeutic Vision Incorporated.

Address correspondence to Dr. Kador.