N-ethyl-N-nitrosourea induces retinal photoreceptor damage in adult rats

Katsuhiko Yoshizawa, Tomo Sasaki, Norihisa Uehara, Maki Kuro, Ayako Kimura, Yuichi Kinoshita, Hisanori Miki, Takashi Yuri, Airo Tsubura

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10 Citations (Scopus)

Abstract

Seven-week-old male Lewis rats received a single intraperitoneal injection of N-ethyl-N-nitrosourea (ENU) (100, 200, 400 or 600 mg/kg), and retinal damage was evaluated 7 days after the treatment. Sequential morphological features of the retina and retinal DNA damage, as determined by a TUNEL assay and phospho-histone H2A.X (γ-H2AX), were analyzed 3, 6, 12, 24 and 72 hr, 7 days, and/or 30 days after 400 mg/kg ENU treatment. Activation of the nuclear enzyme poly (ADP-ribose) polymerase (PARP) was analyzed immunohistochemically by poly (ADP-ribose) (PAR) expression in response to DNA damage of the retina. All rats that received ≥ 400 mg/kg of ENU developed retinal degeneration characterized by the loss of photoreceptor cells in both the central and peripheral retina within 7 days. In the 400 mg/kg ENU-treated rats, TUNEL-positive signals were only located in the photoreceptor cells and peaked 24 hr after ENU treatment. The γ-H2AX signals in inner retinal cells appeared at 24 hr and peaked at 72 hr after ENU treatment, and the PAR signals selectively located in the photoreceptor cell nuclei appeared at 12 hr and peaked at 24 hr after ENU treatment. However, degeneration was restricted to photoreceptor cells, and no degenerative changes in inner retinal cells were seen at any time points. Retinal thickness and the photoreceptor cell ratio in the central and peripheral retina were significantly decreased, and the retinal damage ratio was significantly increased 7 days after ENU treatment. In conclusion, ENU induced retinal degeneration in adult rats that was characterized by photoreceptor cell apoptosis through PARP activity.

Original languageEnglish
Pages (from-to)27-35
Number of pages9
JournalJournal of Toxicologic Pathology
Volume25
Issue number1
DOIs
Publication statusPublished - 2012

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Toxicology

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    Yoshizawa, K., Sasaki, T., Uehara, N., Kuro, M., Kimura, A., Kinoshita, Y., Miki, H., Yuri, T., & Tsubura, A. (2012). N-ethyl-N-nitrosourea induces retinal photoreceptor damage in adult rats. Journal of Toxicologic Pathology, 25(1), 27-35. https://doi.org/10.1293/tox.25.27