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Biogerontology

, Volume 20, Issue 1, pp 109–125 | Cite as

Extensive growth is followed by neurodegenerative pathology in the continuously expanding adult zebrafish retina

  • Jessie Van houcke
  • Emiel Geeraerts
  • Sophie Vanhunsel
  • An Beckers
  • Lut Noterdaeme
  • Marijke Christiaens
  • Ilse Bollaerts
  • Lies De Groef
  • Lieve MoonsEmail author
Research Article
  • 91 Downloads

Abstract

The development of effective treatments for age-related neurodegenerative diseases remains one of the biggest medical challenges today, underscoring the high need for suitable animal model systems to improve our understanding of aging and age-associated neuropathology. Zebrafish have become an indispensable complementary model organism in gerontology research, yet their growth-control properties significantly differ from those in mammals. Here, we took advantage of the clearly defined and highly conserved structure of the fish retina to study the relationship between the processes of growth and aging in the adult zebrafish central nervous system (CNS). Detailed morphological measurements reveal an early phase of extensive retinal growth, where both the addition of new cells and stretching of existent tissue drive the increase in retinal surface. Thereafter, and coinciding with a significant decline in retinal growth rate, a neurodegenerative phenotype becomes apparent,–characterized by a loss of synaptic integrity, an age-related decrease in cell density and the onset of cellular senescence. Altogether, these findings support the adult zebrafish retina as a valuable model for gerontology research and CNS disease modeling and will hopefully stimulate further research into the mechanisms of aging and age-related pathology.

Keywords

Zebrafish Aging Growth Retina Neurogenesis Neurodegeneration 

Abbreviations

Chat

Choline acetyltransferase

CMZ

Ciliary marginal zone

CNS

Central nervous system

DAC

Displaced amacrine cell

DAPI

4′,6-diamidino-2-fenylindool

GCL

Ganglion cell layer

H&E

Haematoxylin and eosin

IHC

Immunohistochemistry

INL

Inner nuclear layer

IPL

Inner plexiform layer

Map2

Microtubule-associated protein 2

NFL

Nerve fiber layer

ONH

Optic nerve head

ONL

Outer nuclear layer

OPL

Outer plexiform layer

OT

Optic tectum

PFA

Paraformaldehyde

PBS

Phosphate buffered saline

PCNA

Proliferating cell nuclear antigen

PKC

Protein kinase C

Psd95

Postsynaptic density protein 95

PRL

Photoreceptor layer

RBPMS

RNA binding protein mRNA processing factor

RGC

Retinal ganglion cell

RPE

Retinal pigment epithelium

SABG

Senescence-associated β-galactosidase

SDS

Sodium dodecyl sulfate

Sv2

Synaptic vesicle protein 2

TH

Tyrosine hydroxylase

ZIRC

Zebrafish International Resource Center

Notes

Acknowledgements

This work has been funded by research Grants from KU Leuven (BOF-OT14/00830), the Research Foundation Flanders (FWO-Vlaanderen, Belgium, G0B2315N and G053217N), and the Hercules Foundation (equipment grants AKUL/09/038 & AKUL/13/09). SV is supported by the Flemish government agency for Innovation by Science and Technology (IWT-Vlaanderen, Belgium), and LDG is a postdoctoral fellow funded by the Research foundation Flanders and KU Leuven.

Compliance with ethical standards

Conflicts of interest

The authors have no actual or potential conflicts of interest.

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Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  • Jessie Van houcke
    • 1
  • Emiel Geeraerts
    • 1
  • Sophie Vanhunsel
    • 1
  • An Beckers
    • 1
  • Lut Noterdaeme
    • 1
  • Marijke Christiaens
    • 1
  • Ilse Bollaerts
    • 1
  • Lies De Groef
    • 1
  • Lieve Moons
    • 1
    Email author return OK on get
  1. 1.Neural Circuit Development and Regeneration Research Group, Animal Physiology and Neurobiology Section, Department of BiologyKU LeuvenLeuvenBelgium

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