Diabetes-Induced Changes in Retinal NAD-Redox Status

Vol. 62, No. 3, 2001

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Original Paper

Diabetes-Induced Changes in Retinal NAD-Redox Status
Phar macological Modulation and Implications for Pathogenesis of Diabetic Retinopathy
Irina G. Obrosova^a, Martin J. Stevens^a, Hans-Jochen Lang^b

^aDivision of Endocrinology and Metabolism, Department of Internal Medicine, University of Michigan Medical Center and the Veteran's Administration, Ann Arbor, Mich., USA;
^bHoechst Marion Roussel Deutschland GmbH, Chemical Research Frankfurt, Frankfurt am Main, Germany

Address of Corresponding Author

Pharmacology 2001;62:172-180 (DOI: 10.1159/000056091)

Key Words

Rat
Retina
Streptozotocin diabetes
Free mitochondrial and cytosolic NAD⁺/NADH ratios
Aldose reductase inhibitor
Sorbitol dehydrogenase inhibitor

Abstract

Diabetes-induced changes in retinal metabolism and function have been linked to increased aldose reductase activity, hypoxia or 'pseudohypoxia' (increase in NADH/NAD⁺ attributed to increased sorbitol dehydrogenase activity). To address this controversy, we evaluated the effects of two vasoactive compounds, alpha ₁-adrenoceptor antagonist prazosin and antioxidant DL- alpha -lipoic acid, as well as sorbitol dehydrogenase inhibitor (SDI-157) and aldose reductase inhibitor (sorbinil) on retinal free mitochondrial and cytosolic NAD⁺/NADH ratios in streptozotocin-diabetic rats. Diabetes-induced decrease in mitochondrial and cytosolic NAD⁺/NADH ratios was completely or partially corrected by prazosin and DL- alpha -lipoic acid (despite the fact that prazosin did not affect and DL- alpha -lipoic acid even further increased sorbitol pathway activity) as well as by sorbinil, whereas SDI-157 was totally ineffective. Hypoxia-like metabolic changes in the diabetic retina originate from aldose reductase, but not sorbitol dehydrogenase activity.

Author Contacts

Dr. Irina G. Obrosova, Division of Endocrinology and Metabolism
Department of Internal Medicine, University of Michigan Medical Center
1150 West Medical Center Drive, MSRB 11, Room 5570
Ann Arbor, MI 48109-0678 (USA)
Tel. +1 734 763 3055, Fax +1 734 662 2349, E-Mail iobrosso@umich.edu

Article Information

Received: Received: February 10, 2000
Accepted: June 5, 2000
Number of Print Pages : 9
Number of Figures : 3, Number of Tables : 1, Number of References : 75

Medline Abstract (ID 11287819)

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