Advertisement

Animal Model for Retinitis Pigmentosa

Retinal Degeneration Induced by N-Methyl-N-Nitrosourea in Rodents and Spontaneous Occurrence in rd Gene Carrying Mice
  • Hiroyuki Nambu
  • Kenshi Yuge
  • Motomaro Nakajima
  • Kanji Takahashi
  • Hirohiko Miki
  • Masanobu Uyama
  • Katsuhiko Yoshizawa
  • Yoshiko Uemura
  • Airo Tsubura

Abstract

N-methyl-N-nitrosourea (MNU) showed a toxic effect on the mouse and rat retinal photoreceptor cells leading to apoptosis. In agreement to human retinitis pigmentosa, the primary event was photoreceptor apoptosis. After photoreceptor cell loss, retinal pigment epithelial (RPE) cell migration to inner retina and accumulation around blood vessels were seen in humans; in rats, the migration was seen, but they were not accumulated around blood vessels, and in mice, RPE migration was not seen. In C3H mice carrying the rd gene as well as C3H mutants (Fas/Fas ligand-deficient mice), retinal degeneration occurred by an apoptotic mechanism. Therefore, Fas/Fas ligand do not play a primary role in the photoreceptor apoptosis in rd gene carrying mice.

Keywords

Retinal Pigment Epithelial Retinal Pigment Epithelial Cell Retinitis Pigmentosa Photoreceptor Cell Retinal Degeneration 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    K.M. Herrold, 1976, Pigmentary degeneration of the retina induced by N-methyl-N-nitrosourea: an experimental study in Syrian hamsters, Arch. Ophthalmol. 78:650–653.Google Scholar
  2. 2.
    A.S.K. Murthy, G.F. Vawter, L. Kopito, and E. Rossen, 1972, Retinal atrophy and cataract following administration of N-methyl-N-nitrosourea, Proc. Soc. Biol. Med. 139:84–87.Google Scholar
  3. 3.
    SB. Smith and K.L. Yielding, 1986, Retinal degeneration in the mouse: a model induced transplacentally by methylnitrosourea, Exp. Eye. Res. 43:791–801.PubMedCrossRefGoogle Scholar
  4. 4.
    H. Nambu, K. Yuge, M. Nakajima, N. Shikata, K. Takahashi, H. Miki, M. Uyama, and A. Tsubura, 1997, Morphologic characteristics of N-methyl-N-nitrosourea-induced retinal degeneration in C57BL mice, Pathol. Int. 47:377–383.PubMedGoogle Scholar
  5. 5.
    M. Nakajima, K. Yuge, H. Senzaki, N. Shikata, H. Miki, M. Uyama, and A. Tsubura, 1996, Photoreceptor apoptosis induced by a single administration of N-methyl-N-nitrosourea in the rat retina, Am. J. Pathol. 148:631–641.PubMedGoogle Scholar
  6. 6.
    K. Yuge, H. Nambu, H. Senzaki, I. Nakao, N. Shikata, K Takahashi, H. Miki, M. Uyama, and A Tsubura, 1996, N-methyl-N-nitrosourea-induced photoreceptor apoptosis in the mouse retina, In Vivo 10:483–486.PubMedGoogle Scholar
  7. 7.
    H. Nambu, K. Yoshizawa, J. Yang, D. Yamamoto, and A. Tsubura, 1998, Age-specific and dose-dependent retinal dysplasia and degeneration induced by a single intraperitoneal administration of N-methyl-N-nitrosourea to rats, Toxicol. Pathol. 11:127–131.CrossRefGoogle Scholar
  8. 8.
    H. Nambu, M. Taomoto, E. Ogura, and A. Tsubura, 1998, Time-specific action of N-methyl-N-nitrosourea in the occurrence of retinal dysplasia and retinal degeneration in neonatal mice, Pathol. Int. 48:199–205.PubMedCrossRefGoogle Scholar
  9. 9.
    M. Nakajima, H. Nambu, N. Shikata, H. Senzaki, H. Miki, and A. Tsubura, 1996, Pigmentary degeneration induced by N-methyl-N-nitrosourea and the fate of pigment epithelial cells in the rat retina, Pathol. Int. 46:874–882.PubMedGoogle Scholar
  10. 10.
    Z.Y. Li, D.E. Possin, and A.H. Milam, 1995, Histopathology of bone spicule pigmentation in retinitis pigmentosa, Ophthalmology 102:805–816.PubMedGoogle Scholar
  11. 11.
    D.W. Caley, C. Johnson, and R.A. Liebelt, 1972, The postnatal development of the retina in the normal and rodless CBA mouse: A light and electron microscopic study, Am. J. Anat 133:179–212.PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic / Plenum Publishers 1999

Authors and Affiliations

  • Hiroyuki Nambu
    • 1
  • Kenshi Yuge
    • 1
  • Motomaro Nakajima
    • 1
  • Kanji Takahashi
    • 1
  • Hirohiko Miki
    • 1
  • Masanobu Uyama
    • 1
  • Katsuhiko Yoshizawa
    • 2
  • Yoshiko Uemura
    • 2
  • Airo Tsubura
    • 2
  1. 1.Department of OphthalmologyKansai Medical UniversityOsakaJapan
  2. 2.Department of PathologyKansai Medical UniversityOsakaJapan

Personalised recommendations