May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Effect of Aldose Reductase Inhibitor Fidarestat on Diabetic Ocular Complications in Spontaneously Diabetic Torii Rats
Author Affiliations & Notes
  • M. Takezawa
    Saitama Medical Center, Jichi Medical University, Saitama-shi, Japan
    Department of Ophthalmology,
  • A. Kakehashi
    Saitama Medical Center, Jichi Medical University, Saitama-shi, Japan
    Department of Ophthalmology,
  • F. Toyoda
    Saitama Medical Center, Jichi Medical University, Saitama-shi, Japan
    Department of Ophthalmology,
  • N. Kinoshita
    Saitama Medical Center, Jichi Medical University, Saitama-shi, Japan
    Department of Ophthalmology,
  • C. Mameuda
    Saitama Medical Center, Jichi Medical University, Saitama-shi, Japan
    Department of Ophthalmology,
  • H. Yamagami
    Saitama Medical Center, Jichi Medical University, Saitama-shi, Japan
    Department of Ophthalmology,
  • N. Kato
    Pharmaceutical Laboratory,Research Department,Sanwa Kagaku Kenkyusyo, Tokyo, Japan
  • S. Ishikawa
    Saitama Medical Center, Jichi Medical University, Saitama-shi, Japan
    Department of Integrated Medicine I,
  • M. Kawakami
    Saitama Medical Center, Jichi Medical University, Saitama-shi, Japan
    Department of Integrated Medicine I,
  • Y. Kanazawa
    Saitama Medical Center, Jichi Medical University, Saitama-shi, Japan
    Department of Integrated Medicine I,
  • Footnotes
    Commercial Relationships  M. Takezawa, None; A. Kakehashi, None; F. Toyoda, None; N. Kinoshita, None; C. Mameuda, None; H. Yamagami, None; N. Kato, None; S. Ishikawa, None; M. Kawakami, None; Y. Kanazawa, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1344. doi:https://doi.org/
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      M. Takezawa, A. Kakehashi, F. Toyoda, N. Kinoshita, C. Mameuda, H. Yamagami, N. Kato, S. Ishikawa, M. Kawakami, Y. Kanazawa; Effect of Aldose Reductase Inhibitor Fidarestat on Diabetic Ocular Complications in Spontaneously Diabetic Torii Rats. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1344. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To evaluate effects of an aldose reductase inhibitor, fidarestat, on development of diabetic retinopathy and cataract in spontaneously diabetic Torii (SDT) rats, an animal model of diabetic ocular complications.

Methods: : The rats were divided as follows: low-dose fidarestat group (8 mg/kg/day, n=14), high-dose fidarestat group (32 mg/kg/day, n=21), and untreated group (n=18). Diabetic retinopathy was evaluated by fluorescein angiomicroscopy and histopathology. Cataract was evaluated by biomicroscopy. Sorbitol levels in the retina and lens and vascular endothelial growth factor (VEGF) levels in ocular fluid were measured 40 weeks after the onset of diabetes.

Results: : Diabetic retinopathy did not develop in the low-dose (0/12 eyes, 0%) (p<0.001) and high-dose fidarestat groups (0/21 eyes, 0%) (p<0.00001) compared with the untreated group (12/17 eyes, 70.6%). Cataract developed less often in the low-dose (4/10 eyes, 40%) (p<0.01) and high-dose fidarestat groups (1/13 eyes, 7.7%) (p<0.00001) compared with the untreated group (12/12 eyes, 100%). Retinal and lens sorbitol levels were lower in the low-dose (2.7±1.1 and 30.0±3.3 nmol/mg protein, n=3, respectively) (p<0.01) and high-dose fidarestat groups (0.7±0.2 and 5.9±0.6 nmol/mg protein, n=4, respectively) (p<0.01) compared with the untreated group (23.2±4.7 nmol/mg protein, n=3). VEGF levels were lower in the low-dose (65.3±4.5 pg/ml, n=6) (p<0.05) and high-dose fidarestat groups (47.7±10 pg/ml, n=9) (p<0.01) compared with the untreated group (324.7±76.4 pg/ml, n=8).

Conclusions: : Fidarestat reduced the levels of sorbitol in the retina and lens and VEGF levels in the ocular fluid. Fidarestat prevented or delayed development of diabetic retinopathy and cataract in SDT rats.

Keywords: diabetic retinopathy 
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