Characteristics of rod regeneration in a novel zebrafish retinal degeneration model using N-methyl-N-nitrosourea (MNU)

Tappeiner, Christoph; Balmer, Jasmin; Iglicki, Matias; Schuerch, Kaspar; Jazwinska, Anna; Enzmann, Volker; Tschopp, Markus (2013). Characteristics of rod regeneration in a novel zebrafish retinal degeneration model using N-methyl-N-nitrosourea (MNU). PLoS ONE, 8(8), e71064. Public Library of Science 10.1371/journal.pone.0071064

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ophthalmology

UniBE Contributor:

Tappeiner, Christoph; Balmer, Jasmin; Schürch, Kaspar Werner; Enzmann, Volker and Tschopp, Markus

Subjects:

600 Technology > 610 Medicine & health
500 Science

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

Sebastian Wolf

Date Deposited:

03 Mar 2014 14:51

Last Modified:

05 Dec 2014 23:17

Publisher DOI:

10.1371/journal.pone.0071064

PubMed ID:

23951079

BORIS DOI:

10.7892/boris.42810

URI:

https://boris.unibe.ch/id/eprint/42810

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