May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Prevention of Diabetic Ocular Complications in Spontaneously Diabetic Torii Rats by Aldose Reductase Inhibitor Fidarestat
Author Affiliations & Notes
  • A. Kakehashi
    Ophthalmology,
    Omiya Med Ctr Jichi Med Sch, Saitama–Shi, Japan
  • Y. Saito
    Ophthalmology,
    Omiya Med Ctr Jichi Med Sch, Saitama–Shi, Japan
  • R. Ono
    Ophthalmology,
    Omiya Med Ctr Jichi Med Sch, Saitama–Shi, Japan
  • N. Sugi
    Ophthalmology,
    Omiya Med Ctr Jichi Med Sch, Saitama–Shi, Japan
  • K. Mori
    Ophthalmology,
    Omiya Med Ctr Jichi Med Sch, Saitama–Shi, Japan
  • M. Kuroki
    Integrated Medicine I,
    Omiya Med Ctr Jichi Med Sch, Saitama–Shi, Japan
  • M. Kawakami
    Integrated Medicine I,
    Omiya Med Ctr Jichi Med Sch, Saitama–Shi, Japan
  • Y. Kanazawa
    Integrated Medicine I,
    Omiya Med Ctr Jichi Med Sch, Saitama–Shi, Japan
  • H. Hirooka
    Drug Development Research Laboratories, Sanwa Kagaku Kenkyusho, Mie, Japan
  • N. Kato
    Drug Development Research Laboratories, Sanwa Kagaku Kenkyusho, Mie, Japan
  • Footnotes
    Commercial Relationships  A. Kakehashi, Sanwa Kagaku Kenkyusho Co., Ltd. F; Y. Saito, None; R. Ono, None; N. Sugi, None; K. Mori, None; M. Kuroki, None; M. Kawakami, None; Y. Kanazawa, None; H. Hirooka, None; N. Kato, None.
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 3248. doi:
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      A. Kakehashi, Y. Saito, R. Ono, N. Sugi, K. Mori, M. Kuroki, M. Kawakami, Y. Kanazawa, H. Hirooka, N. Kato; Prevention of Diabetic Ocular Complications in Spontaneously Diabetic Torii Rats by Aldose Reductase Inhibitor Fidarestat . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3248.

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

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Abstract

Abstract: : Purpose:To evaluate the effects of an aldose reductase inhibitor, fidarestat, on the development of diabetic retinopathy and cataract in spontaneously diabetic Torii (STD) rats, which provide an excellent animal model of diabetic ocular complications (Shinohara M et al.: A new spontaneously diabetic non–obese Torii rat strain with severe ocular complications. Int Jnl Experimental Diab Res 1, 2000). Methods: The rats were divided into two groups, the fidarestat–treated group (16 mg/kg/day) (n=15) and the untreated group (n=10). Sorbitol levels were measured by HPLC in the lens and the retina at ages 36, 52, 55, and 58 weeks. Slit–lamp biomicroscopy and pathological study were also performed. Results: At 36 weeks, sorbitol levels were markedly lower in the treated eyes (n=3) than in the untreated eyes (n=3) both in the retina (599.7±293.1 vs. 3853.3±1022.5 ng/mg) (p=0.006) and lens (221.7±172.1 vs. 1368.0±598.6 ng/mg) (p=0.03). The reduction of the sorbitol levels in the treated group compared to the untreated group persisted through the experimental periods: 513.5±228.5 vs. 6363.3±4371.8 ng/mg in the retina (p=0.04) and 235.5±114.7 vs. 2493.3±906.7 ng/mg in the lens (p=0.004) at age 52 weeks. No cataracts were observed in the treated group (0/15 rats) at 35 weeks when 10 of 10 rats in the untreated group developed it. However, cataracts developed even in the treated group by 52 weeks (15/15 rats, 100%). Diabetic retinopathy (diabetic tractional retinal detachment) began to be observed after 36 weeks in both groups. However, the incidence was significantly lower in the treated group (2/12 eyes, 16.7%) than in the untreated group (5/7 eyes, 71.4%) when evaluated by pathological examination after 52 weeks (52–58 weeks) of age. Conclusions: Fidarestat reduced the levels of sorbitol in the retina and lens and prevented or delayed development of ocular complications in SDT rats.

Keywords: diabetic retinopathy • retina • pathobiology 
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