PUBLICATION

Characteristics of Rod Regeneration in a Novel Zebrafish Retinal Degeneration Model Using N-Methyl-N-Nitrosourea (MNU)

Authors
Tappeiner, C., Balmer, J., Iglicki, M., Schuerch, K., Jazwinska, A., Enzmann, V., and Tschopp, M.
ID
ZDB-PUB-130904-2
Date
2013
Source
PLoS One   8(8): e71064 (Journal)
Registered Authors
Jazwinska, Anna, Tschopp, Markus
Keywords
Zebrafish, Photoreceptors, Retina, Cell staining, Neurobiology of disease and regeneration, Eyes, Retinal degeneration, Histology
MeSH Terms
  • Animals
  • Apoptosis
  • Cell Proliferation/drug effects
  • Disease Models, Animal
  • Methylnitrosourea/toxicity*
  • Neuroglia
  • Regeneration*
  • Retina/metabolism
  • Retina/pathology
  • Retinal Degeneration/chemically induced*
  • Retinal Degeneration/pathology*
  • Retinal Rod Photoreceptor Cells/pathology
  • Retinal Rod Photoreceptor Cells/physiology*
  • Rhodopsin
  • Zebrafish/physiology*
PubMed
23951079 Full text @ PLoS One
Abstract

Primary loss of photoreceptors caused by diseases such as retinitis pigmentosa is one of the main causes of blindness worldwide. To study such diseases, rodent models of N-methyl-N-nitrosourea (MNU)-induced retinal degeneration are widely used. As zebrafish (Danio rerio) are a popular model system for visual research that offers persistent retinal neurogenesis throughout the lifetime and retinal regeneration after severe damage, we have established a novel MNU-induced model in this species. Histology with staining for apoptosis (TUNEL), proliferation (PCNA), activated Müller glial cells (GFAP), rods (rhodopsin) and cones (zpr-1) were performed. A characteristic sequence of retinal changes was found. First, apoptosis of rod photoreceptors occurred 3 days after MNU treatment and resulted in a loss of rod cells. Consequently, proliferation started in the inner nuclear layer (INL) with a maximum at day 8, whereas in the outer nuclear layer (ONL) a maximum was observed at day 15. The proliferation in the ONL persisted to the end of the follow-up (3 months), interestingly, without ongoing rod cell death. We demonstrate that rod degeneration is a sufficient trigger for the induction of Müller glial cell activation, even if only a minimal number of rod cells undergo cell death. In conclusion, the use of MNU is a simple and feasible model for rod photoreceptor degeneration in the zebrafish that offers new insights into rod regeneration.

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