To investigate a possible role of excessive polyol production in the pathogenesis of diabetic retinopathy, 16 ALX-induced diabetic dogs and 20 experimentally galactosemic dogs were randomly assigned to 5 yr of treatment with either sorbinil, an aldose reductase inhibitor, or a placebo. The severity of hyperglycemia in sorbinil-treated and placebo groups was monitored throughout the 5-yr study by assay of glycosuria and nonenzymatically glycated plasma protein and HbA1 needed in an effort to avoid confounding possible group differences in hyperglycemia severity with possible drug effects. Inhibition of polyol production by sorbinil was monitored in erythrocytes throughout the study and also in retina and other tissue obtained at autopsy. Trypsin digests of retinal vessels were compared after 60 mo of diabetes and after 42 and 60 mo of galactosemia. In diabetic dogs, development of retinopathy was not significantly influenced by a sorbinil dose (20 mg · kg−1 · day−1) sufficient to prevent elevation of sorbitol levels in retina and other tissue. Likewise, in dogs made experimentally galactosemic for 42–60 mo, administration of sorbinil (60–80 mg · kg−1 day−1) had no significant effect on the development of retinopathy notwithstanding prevention of 93–96% of the polyol elevation in retina and other tissue. Retinal capillary basement membrane was significantly thicker than normal in diabetic and in galactosemic dogs and was not significantly influenced by administration of sorbinil in either dog model. Thus, no evidence was found that the development of retinopathy is critically dependent on excessive polyol production or accumulation.
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Original Articles|
June 01 1993
Aldose Reductase Inhibition Fails to Prevent Retinopathy in Diabetic and Galactosemic Dogs
Ronald L Engerman;
Ronald L Engerman
Department of Ophthalmology, University of Wisconsin-Madison
Madison, Wisconsin
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Timothy S Kern
Timothy S Kern
Department of Ophthalmology, University of Wisconsin-Madison
Madison, Wisconsin
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Address correspondence and reprint requests to Dr. Ronald L. Engerman, Department of Ophthalmology, University of Wisconsin, 1300 University Avenue, Madison, Wl 53706–1532.
Diabetes 1993;42(6):820–825
Article history
Received:
November 04 1992
Revision Received:
January 14 1993
Accepted:
January 14 1993
PubMed:
8495805
Citation
Ronald L Engerman, Timothy S Kern; Aldose Reductase Inhibition Fails to Prevent Retinopathy in Diabetic and Galactosemic Dogs. Diabetes 1 June 1993; 42 (6): 820–825. https://doi.org/10.2337/diab.42.6.820
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