A diabetic-like thickening of retinal capillary basement membranes induced in rats fed for 207 consecutive days a diet containing 50% galactose was prevented by the addition to the diet of tolrestat, a potent, structurally novel inhibitor of aldose reductase. Analysis of electron micrographs (× 25,000) of capillaries from the outer plexiform layer of the retina by computer planimetry showed that the basement membranes were approximately twofold thicker in rats fed galactose than in those fed either a standard diet or a diet containing galactose and tolrestat in doses of 43 or 57 mg/kg/day. The thickening of basement membranes in galactosefed rats was accompanied by other ultrastructural alterations mimicking changes typical of diabetic microangiopathy, such as multilamination and the formation of vacuoles and dense inclusions. Therefore, the galactosemic rat represents a useful model for studying basement membrane-related complications of diabetes and their possible prevention by aldose reductase inhibitors.
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Original Contributions|
March 01 1986
Prevention of Basement Membrane Thickening in Retinal Capillaries by a Novel Inhibitor of Aldose Reductase, Tolrestat
W Gerald Robison, Jr;
W Gerald Robison, Jr
National Eye Institute, NIH
Bethesda, Maryland
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Peter F Kador;
Peter F Kador
National Eye Institute, NIH
Bethesda, Maryland
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Yoshio Akagi;
Yoshio Akagi
National Eye Institute, NIH
Bethesda, Maryland
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Jin H Kinoshita;
Jin H Kinoshita
National Eye Institute, NIH
Bethesda, Maryland
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Ramona Gonzalez;
Ramona Gonzalez
Ayerst Research Laboratories, Inc.
CN 8000, Princeton, New Jersey
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Dushan Dvornik
Dushan Dvornik
Ayerst Research Laboratories, Inc.
CN 8000, Princeton, New Jersey
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Address reprint requests to Dr. W. G. Robison, Jr., Bldg. 9, Rm. 1E104, National Eye Institute, NIH, Bethesda, Maryland 20842.
Diabetes 1986;35(3):295–299
Article history
Received:
April 18 1985
Revision Received:
July 08 1985
Citation
W Gerald Robison, Peter F Kador, Yoshio Akagi, Jin H Kinoshita, Ramona Gonzalez, Dushan Dvornik; Prevention of Basement Membrane Thickening in Retinal Capillaries by a Novel Inhibitor of Aldose Reductase, Tolrestat. Diabetes 1 March 1986; 35 (3): 295–299. https://doi.org/10.2337/diab.35.3.295
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