title: Methylnitrosourea (MNU)-induced retinal degeneration and regeneration in the zebrafish: histological and functional characteristics.
abstract: Retinal degenerative diseases, e.g. retinitis pigmentosa, with resulting photoreceptor damage account for the majority of vision loss in the industrial world. Animal models are of pivotal importance to study such diseases. In this regard the photoreceptor-specific toxin N-methyl-N-nitrosourea (MNU) has been widely used in rodents to pharmacologically induce retinal degeneration. Previously, we have established a MNU-induced retinal degeneration model in the zebrafish, another popular model system in visual research. A fascinating difference to mammals is the persistent neurogenesis in the adult zebrafish retina and its regeneration after damage. To quantify this observation we have employed visual acuity measurements in the adult zebrafish. Thereby, the optokinetic reflex was used to follow functional changes in non-anesthetized fish. This was supplemented with histology as well as immunohistochemical staining for apoptosis (TUNEL) and proliferation (PCNA) to correlate the developing morphological changes. In summary, apoptosis of photoreceptors occurs three days after MNU treatment, which is followed by a marked reduction of cells in the outer nuclear layer (ONL). Thereafter, proliferation of cells in the inner nuclear layer (INL) and ONL is observed. Herein, we reveal that not only a complete histological but also a functional regeneration occurs over a time course of 30 days. Now we illustrate the methods to quantify and follow up zebrafish retinal de- and regeneration using MNU in a video-format.
authors.affiliation: Department of Ophthalmology, Inselspital, University of Bern.
authors.forename: Ellinor
authors.initials: E
authors.lastname: Maurer
authors.affiliation: Department of Ophthalmology, Inselspital, University of Bern; Department of Ophthalmology, University Hospital of Basel.
authors.forename: Markus
authors.initials: M
authors.lastname: Tschopp
authors.affiliation: Department of Ophthalmology, Inselspital, University of Bern.
authors.forename: Christoph
authors.initials: C
authors.lastname: Tappeiner
authors.affiliation: Department of Biology, University of Fribourg.
authors.forename: Pauline
authors.initials: P
authors.lastname: Sallin
authors.affiliation: Department of Biology, University of Fribourg.
authors.forename: Anna
authors.initials: A
authors.lastname: Jazwinska
authors.affiliation: Department of Ophthalmology, Inselspital, University of Bern; volker.enzmann@insel.ch.
authors.forename: Volker
authors.initials: V
authors.lastname: Enzmann
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D008770:Methylnitrosourea; D010786:Photoreceptor Cells / Q000187:drug effects / Q000473:pathology; D012038:Regeneration / Q000502:physiology*; D012160:Retina / Q000187:drug effects* / Q000502:physiology*; D012162:Retinal Degeneration / Q000139:chemically induced* / Q000473:pathology*; D015027:Zebrafish
chemical_list: D008770:Methylnitrosourea