Characteristics of rod regeneration in a novel zebrafish retinal degeneration model using N-methyl-N-nitrosourea (MNU).
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.
Department of Ophthalmology, Inselspital, University of Bern, Bern, Switzerland.
Christoph
C
Tappeiner
Jasmin
J
Balmer
Matias
M
Iglicki
Kaspar
K
Schuerch
Anna
A
Jazwinska
Volker
V
Enzmann
Markus
M
Tschopp
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D008770:Methylnitrosourea / Q000633:toxicity*; D009457:Neuroglia; D012038:Regeneration; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012162:Retinal Degeneration / Q000139:chemically induced* / Q000473:pathology*; D017948:Retinal Rod Photoreceptor Cells / Q000473:pathology / Q000502:physiology*; D012243:Rhodopsin; D015027:Zebrafish / Q000502:physiology*
D008770:Methylnitrosourea; D012243:Rhodopsin