June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Adult zebrafish atoh7 mutants lack retinal ganglion cells resulting in structural changes of the optic tectum and altered social interactions
Author Affiliations & Notes
  • Juliane Hammer
    Developmental Genetics, Center for Regenerative Therapies Dresden, Zentrum fur Regenerative Therapien Dresden, Dresden, Sachsen, DE, academic/medres, Dresden, Sachsen, Germany
  • Paul Röppenack
    Developmental Genetics, Center for Regenerative Therapies Dresden, Zentrum fur Regenerative Therapien Dresden, Dresden, Sachsen, DE, academic/medres, Dresden, Sachsen, Germany
  • Sarah Yousuf
    Developmental Genetics, Center for Regenerative Therapies Dresden, Zentrum fur Regenerative Therapien Dresden, Dresden, Sachsen, DE, academic/medres, Dresden, Sachsen, Germany
  • Heiner Grandel
    Developmental Genetics, Center for Regenerative Therapies Dresden, Zentrum fur Regenerative Therapien Dresden, Dresden, Sachsen, DE, academic/medres, Dresden, Sachsen, Germany
  • Anja Machate
    Developmental Genetics, Center for Regenerative Therapies Dresden, Zentrum fur Regenerative Therapien Dresden, Dresden, Sachsen, DE, academic/medres, Dresden, Sachsen, Germany
  • Marika Fischer
    Developmental Genetics, Center for Regenerative Therapies Dresden, Zentrum fur Regenerative Therapien Dresden, Dresden, Sachsen, DE, academic/medres, Dresden, Sachsen, Germany
  • Stefan Hans
    Developmental Genetics, Center for Regenerative Therapies Dresden, Zentrum fur Regenerative Therapien Dresden, Dresden, Sachsen, DE, academic/medres, Dresden, Sachsen, Germany
  • Michael Brand
    Developmental Genetics, Center for Regenerative Therapies Dresden, Zentrum fur Regenerative Therapien Dresden, Dresden, Sachsen, DE, academic/medres, Dresden, Sachsen, Germany
  • Footnotes
    Commercial Relationships   Juliane Hammer None; Paul Röppenack None; Sarah Yousuf None; Heiner Grandel None; Anja Machate None; Marika Fischer None; Stefan Hans None; Michael Brand None
  • Footnotes
    Support  DFG BR 1746/3 and 1746/6, ERC advanced grant Zf-BrainReg, PhD scholarship Studienstiftung des deutschen Volkes
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4583 – F0445. doi:
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      Juliane Hammer, Paul Röppenack, Sarah Yousuf, Heiner Grandel, Anja Machate, Marika Fischer, Stefan Hans, Michael Brand; Adult zebrafish atoh7 mutants lack retinal ganglion cells resulting in structural changes of the optic tectum and altered social interactions. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4583 – F0445.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Atoh7 plays a major role in the development of retinal ganglion cells and the optic nerve and mutations in ATOH7 have been associated with multiple ocular disease traits in humans. In zebrafish, atoh7 mutants fail to generate retinal ganglion cells during embryogenesis, until 6 days post fertilization. Here we characterized adult atoh7 mutants to explore the consequences of missing retinal output on retinal and tectal structure, as well as visually-mediated behaviors.

Methods : We raised atoh7 mutants to adulthood under adjusted feeding and holding conditions and systematically characterized their phenotype at 10 to 12 months of age. The histological structure of retina and tectum was monitored using histology and immunohistochemistry. We performed measurements of retinal thickness and analysis of blood vessel distribution using optical coherence tomography. Further, visually-mediated behavior was assessed using a dark-light place preference test, a social preference test, and the optokinetic response assay. The influence of vision on shoaling behavior was analyzed using the idTracker software.

Results : Adult atoh7 mutants display a darker body pigmentation and significantly reduced body size. Likewise, their retina is significantly thinner (more than 10 %) as they lack all retinal ganglion cells, and therefore, neither possess a nerve fiber layer, nor form an optic nerve. In addition, the distribution of retinal blood vessels is altered in atoh7 mutants. The optic tectum of atoh7 mutants is reduced in size by 25 % and contains less white matter, as well as exhibits a disrupted layering. Applied behavioral assays confirm that adult atoh7 mutants are blind, and show changes in their social behavior.

Conclusions : We find that retinal ganglion cells are still lacking at the adult stage of zebrafish atoh7 mutants resulting in the absence of the optic nerve and a failure of the optokinetic response. Moreover, we conclude that missing innervations of the optic tectum and the associated lack of visual input are the likely cause of structural changes of the optic tectum and subsequent alterations in social interactions.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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