Involvement of neuronal nitric oxide synthase in N-methyl-N-nitrosourea-induced retinal degeneration in mice

J Pharmacol Sci. 2015 Mar;127(3):394-6. doi: 10.1016/j.jphs.2015.02.008. Epub 2015 Feb 17.

Abstract

N-methyl-N-nitrosourea (MNU) is widely used to study the mechanism of retinal degenerative diseases (RDs) because of its selectivity of photoreceptor cell death. Many reports suggest that excessive nitric oxide (NO) plays a crucial role in neuronal cell death. We hypothesized that nitric oxide synthase (NOS)/NO are involved in photoreceptor cell death by MNU. We found that the levels of NO increased after MNU treatment. Furthermore, we demonstrated that neuronal NOS specific inhibitor attenuated photoreceptor cell death by MNU in mice. We believe that our findings might be a new target for the treatment of RDs.

Keywords: Neurotoxicity; Nitric oxide; Retina.

MeSH terms

  • Animals
  • Cell Death / drug effects
  • Cell Death / genetics
  • Enzyme Inhibitors / therapeutic use
  • Male
  • Methylnitrosourea* / toxicity
  • Mice, Inbred C57BL
  • Molecular Targeted Therapy
  • Nitric Oxide / physiology
  • Nitric Oxide Synthase Type I / antagonists & inhibitors
  • Nitric Oxide Synthase Type I / physiology*
  • Photoreceptor Cells / drug effects
  • Photoreceptor Cells / pathology
  • Retinal Degeneration / chemically induced
  • Retinal Degeneration / drug therapy
  • Retinal Degeneration / genetics*
  • Retinal Degeneration / pathology
  • Thiourea / analogs & derivatives
  • Thiourea / therapeutic use

Substances

  • Enzyme Inhibitors
  • ethyl (4-(trifluoromethyl)phenyl)carbamimidothioate
  • Nitric Oxide
  • Methylnitrosourea
  • Nitric Oxide Synthase Type I
  • Thiourea