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Fumihiko Toyoda, Akihiro Kakehashi, Hiroko Takano, Nozomi Kinoshita, Machiko Shimmura-Tomita, Ayumi Ota, Yoshiaki Tanaka, Takafumi Matsumoto, Junichi Tsuji; EFFECT OF RANIRESTAT, A NEW ALDOSE REDUCTASE INHIBITOR, ON DIABETIC RETINOPATHY IN SDT RATS. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1060.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the effect of ranirestat (AS3201, Dainippon Sumitomo Pharmaceutical Co., Ltd., Osaka, Japan), a new aldose reductase inhibitor (ARI), on diabetic retinopathy in Spontaneously Diabetic Torii (SDT) Rats.
We tested two different ARIs, ranirestat and epalrestat (Kinedak, Ono Pharmaceutical Co., Ltd., Osaka, Japan) in this experiment. The animals were divided into 6 groups, normal Sprague-Dawley rats (n=8), untreated SDT rats (n=9), ranirestat-treated SDT rats (0.1, 1.0, 10 mg/kg/day, n=7, 8, 6, respectively), 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. The eyes then were enucleated for conventional histopathologic and immunohistochemical studies. The retinal thickness and the area of the stained glial fibrillary acidic protein (GFAP) in the retina in an area 300 microns wide were measured using ImageJ.
The mean retinal thickness was 114.6±25.6 µm in the normal group, 191.3±31.2 in the untreated group, 132.4±45.0 in the 0.1 mg/kg/day ranirestat group, 119.2±25.2 in the 1.0 mg/kg/day ranirestat group, 127.3±31.6 in the 10 mg/kg/day ranirestat group, and 155.3±27.9 in the epalrestat group. The retinas in the untreated group were significantly thicker than those in the normal and ranirestat (0.1, 1.0, 10 mg/kg/day) groups (P=0.0012, 0.0316, 0.0027, 0.0227, respectively). The mean area of stained GFAP was 550.7±282.2 µm2 in the normal group, 1,502.7±826.3 in the untreated group, 1,038.3±756.0 in the 0.1 mg/kg/day ranirestat group, 484.0±384.7 in the 1.0 mg/kg/day ranirestat group, 596.1±360.2 in the 10 mg/kg/day ranirestat group, and 1,970.7±1049.8 in the epalrestat group. The stained area in the untreated group was significantly larger than in the normal and ranirestat (1.0 mg/kg/day) groups (P=0.0251, P=0.0405, respectively). The stained area in the epalrestat group was significantly larger than that in the normal group (P=0.0480).
Ranirestat reduced the retinal thickness and the area of stained GFAP in SDT rats and might suppress diabetic retinopathy and have a neuroprotective effect on the retina in SDT rats.
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