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2001 Fiscal Year Final Research Report Summary

Photoreceptor apoptosis control in animal models for retinitis pigmentosa by caspase inhibitor

Research Project

Project/Area Number 12671728
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionKansai Medical University

Principal Investigator

TSUBURA Airo  Kansai Med.Univ.,Faculty of Medicine,Progessor, 医学部, 教授 (90098137)

Co-Investigator(Kenkyū-buntansha) HAGA Satomi  Nara Med.Univ., Faculty of Medicine, Assistant Professor, 医学部, 講師 (20192263)
MIKI Hirohiko  Kansai Med.Univ., Faculty of Medicine, Associate Professor, 医学部, 助教授 (30077771)
SHIKATA Nobuaki  Kansai Med.Univ., Faculty of Medicine, Associate Professor, 医学部, 助教授 (00121939)
Project Period (FY) 2000 – 2001
KeywordsRetinitis pigmentosa / N-methy1-N-nitrosourea / Apoptosis / Photoreceptor cell / Retinal degeneration / rd gene / Caspase / Caspase inhibitor
Research Abstract

The effect of a caspase-3 inhibitor on photoreceptor apoptosis was investigated. Sixty mg/kg MNU was given intraperitoneally to 50 day old female Sprague-Dawley rats, and 4000 ng Ac-DEVD-CHO, a caspase-3 inhibitor, was injected intravitreally twice at 0 and 10 hr after MNU. In MNU-treated rats, the TUNEL index 24hr post-MNU was 79.5% in the peripheral and 83.7% in the central retina, while the Ac-DEVD-CHO injection significantly reduced it to 59.7% and 71.8%, respectively. Total retinal thickness 7 days after MNU was 38 μm in the peripheral and 75 μm in the central retina. Ac-DEVD-CHO injection increased these values to 72 and 77 μm, respectively. The retinal damage ratio 7 days after MNU was 98.5 %. Ac-DEVD-CHO injection significantly reduced this value to 54.4%, In C3H mice carrying the rd gene, 2 mg/kg of Ac-DEVD-CHO was injected intraperitoneally every other day from 8 days of age, and retinal damage was compared with that in saline-treated mice at 13 days and 17 days of age. At 13 days of age, total and outer retinal thickness in saline-treated mice was 140.3 μm and 37.5 μm, compared with 160.4 μm and 49.5 μm, respectively, in Ac-DEVD-CHO-treated mice (p<0.01, respectively)> However, at 17 days of age, Ac-DEVD-CHO treatment did not ameliorate retinal degeneration. In Both models, the caspase-3 inhibitor was partially effective in suppressing retinal degeneration through inhibition of the apoptosis of photoreceptor cells.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Yoshizawa K: "Caspase-3 inhibitor rescues N-methyl-N-nitrosourea-induced retinal degeneration in Sprague-Dawley rats"Exp Eye Res.. 71(6). 629-635 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yang J: "Retinal damage induced by cisplatin in neonatal rats and mice"Cuff Eye Res. 20(6). 441-446 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshizawa K: "Cataractogenesis in neonatal Sprague-Dawley rats by N-methyl-N-nitrosourea"Toxicol Pathol. 28(4). 555-564 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshizawa K: "Caspase-3 inhibitor transiently delays inherited retinal degeneration in C3H mice carrying the rd gene"Graefes Arch.Clin.Exp.Ophthalmol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshizawa K, Yang J, Senzaki H, Uemura Y, Kiyozuka Y, Shikata N, Oishi Y, Miki H and Tubura A: "Caspase-3 inhibitor rescues N-methyl-N-nitrosouren-induced retinal degeneration in Sprague-Dawley rats"Exp Eye Res. 71(6). 629-635 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yang J, Yoshizawa K, Shikata N, Kiyozuka Y, Senzaki H and Tubura A: "Retinal damage induced by cisplatin in neonatal rats and mice."Curr Eye Res. 20(6). 441-446 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshizawa K, Oishi Y, Nambu H, Yamamoto D, Yang J, Senzaki H, Miki H and Tsubura A: "Cataractogenesis in neonatal Sprague-Dawley rats by N-methyl-N-nitrosourea."Toxicol Pathol. 28(4). 555-564 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshizawa K, Kiuchi K, Nambu H, Yang J, Senzaki H, Kiyozuka Y, Shikata N and Tsubura A.: "Caspase-3 inhibitor transiently delays inherited retinal degeneration in C3H mice carying the rd gene"Graefes Arch Clin Exp Ophthalmol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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