Dose-Dependent Reduction of Retinal Vessel Changes Associated with Diabetic Retinopathy in Galactose-Fed Dogs by the Aldose Reductase Inhibitor M79175

To investigate the role of increased polyol pathway activity and hemodynamic deficits in the pathogenesis of diabetic retinopathy in non-insulin-dependent diabetes mellitus (NIDDM), Otsuka Long-Evans Tokushima fatty (OLETF) rats, an animal model of human NIDDM, were given water with or without 30% sucrose and some of them were fed laboratory chow containing 0.03% cilostazol, an anticoagulant, or 0.05% [5-(3-thienyl)tetrazol-1-yl] acetic acid monohydrate (TAT), an aldose reductase inhibitor, for 8 wk. Long-Evans Tokushima Otsuka (LETO) rats were used as nondiabetic controls. The peak latencies of oscillatory potentials of the electroretinogram in sucrose-fed OLETF rats were significantly prolonged compared with those in OLETF rats without sucrose feeding and LETO rats. There was a marked increase in platelet aggregability and a significant decrease in erythrocyte 2,3-diphosphoglycerate in sucrose-fed OLETF rats. Cilostazol significantly improved these parameters without changes in retinal levels of sorbitol and fructose. TAT, however, ameliorated all of these parameters. These findings confirm that the sucrose-fed OLETF rat is a useful animal model of retinopathy in human NIDDM and suggest that cilostazol improved diabetic retinopathy by modifying vascular factors, not by altering polyol pathway activity.

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Dose-Dependent Prevention of Sugar Cataracts in Galactose-fed Dogs by the Aldose Reductase Inhibitor M79175

Experimental Eye Research ◽

10.1006/exer.1997.0412 ◽

1998 ◽

Vol 66 (2) ◽

pp. 217-222 ◽

Cited By ~ 26

Author(s):

SANAI SATO ◽

KAZUHIKO MORI ◽

MILTON WYMAN ◽

PETER F. KADOR

Keyword(s):

Aldose Reductase ◽

Reductase Inhibitor ◽

Aldose Reductase Inhibitor ◽

Dose Dependent

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Effect of Ranirestat, a New Aldose Reductase Inhibitor, on Diabetic Retinopathy in SDT Rats

Journal of Diabetes Research ◽

10.1155/2014/672590 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 9

Author(s):

Fumihiko Toyoda ◽

Yoshiaki Tanaka ◽

Ayumi Ota ◽

Machiko Shimmura ◽

Nozomi Kinoshita ◽

...

Keyword(s):

Diabetic Retinopathy ◽

Aldose Reductase ◽

Reductase Inhibitor ◽

Retinal Thickness ◽

Neuroprotective Effect ◽

Treated Group ◽

Aldose Reductase Inhibitor ◽

Untreated Group ◽

Sprague Dawley ◽

Sprague Dawley Rats

Purpose. To evaluate the effect of ranirestat, a new aldose reductase inhibitor (ARI), on diabetic retinopathy (DR) in Spontaneously Diabetic Torii (SDT) rats.Methods. The animals were divided into six groups, normal Sprague-Dawley rats(n=8), untreated SDT rats(n=9), ranirestat-treated SDT rats (0.1, 1.0, and 10 mg/kg/day,n=7, 8, and 6, resp.), and epalrestat-treated SDT rats (100 mg/kg/day,n=7). Treated rats received oral ranirestat or epalrestat once daily for 40 weeks after the onset of diabetes. After the eyes were enucleated, the retinal thickness and the area of stained glial fibrillary acidic protein (GFAP) were measured.Results. The retinas in the untreated group were significantly thicker than those in the normal and ranirestat-treated (0.1, 1.0, and 10 mg/kg/day) groups. The immunostained area of GFAP in the untreated group was significantly larger than that in the normal and ranirestat-treated (1.0 and 10 mg/kg/day) groups. There were no significant differences between the untreated group and epalrestat-treated group in the retinal thickness and the area of stained GFAP.Conclusion. Ranirestat reduced the retinal thickness and the area of stained GFAP in SDT rats and might suppress DR and have a neuroprotective effect on diabetic retinas.

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