April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
EFFECT OF RANIRESTAT, A NEW ALDOSE REDUCTASE INHIBITOR, ON DIABETIC RETINOPATHY IN SDT RATS
Author Affiliations & Notes
  • Fumihiko Toyoda
    Department of Ophthalmology, Jichi Medical University,Saitama Medical Center, Saitama, Japan
  • Akihiro Kakehashi
    Department of Ophthalmology, Jichi Medical University,Saitama Medical Center, Saitama, Japan
  • Hiroko Takano
    Department of Ophthalmology, Jichi Medical University,Saitama Medical Center, Saitama, Japan
  • Nozomi Kinoshita
    Department of Ophthalmology, Jichi Medical University,Saitama Medical Center, Saitama, Japan
  • Machiko Shimmura-Tomita
    Department of Ophthalmology, Jichi Medical University,Saitama Medical Center, Saitama, Japan
  • Ayumi Ota
    Department of Ophthalmology, Jichi Medical University,Saitama Medical Center, Saitama, Japan
  • Yoshiaki Tanaka
    Department of Ophthalmology, Jichi Medical University,Saitama Medical Center, Saitama, Japan
  • Takafumi Matsumoto
    Drug Development Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd, Osaka, Japan
  • Junichi Tsuji
    Drug Development Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd, Osaka, Japan
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1060. doi:
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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)

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Abstract
 
Purpose
 

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.

 
Methods
 

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.

 
Results
 

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).

 
Conclusions
 

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.

 
 
The retinas in each group. Brown region shows stained GFAP.<A>Normal group Untreated group <C>Ranirestat group (1.0mg/kg/day) <D> Epalrestat group
 
The retinas in each group. Brown region shows stained GFAP.<A>Normal group Untreated group <C>Ranirestat group (1.0mg/kg/day) <D> Epalrestat group
 
Keywords: 499 diabetic retinopathy • 615 neuroprotection • 554 immunohistochemistry  
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