June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
A comparative analysis of gene and protein expression in a zebrafish model of chronic photoreceptor degeneration
Author Affiliations & Notes
  • Ashley Kramer
    Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, Michigan, United States
  • Justin Carthage
    Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, Michigan, United States
  • Marla Spain
    Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan, United States
  • Katherine Gurdziel
    Genome Sciences Core, Wayne State University, Detroit, Michigan, United States
  • Tiffany A. Cook
    Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan, United States
    Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, Michigan, United States
  • Ryan Thummel
    Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, Michigan, United States
  • Footnotes
    Commercial Relationships   Ashley Kramer None; Justin Carthage None; Marla Spain None; Katherine Gurdziel None; Tiffany Cook None; Ryan Thummel None
  • Footnotes
    Support  NEI Core Grant P30EY04068 (Linda Hazlett), NEI R01EY026551 (Ryan Thummel), NEI F30EY0311142 (Ashley Kramer), NEI R21EY031526 (Tiffany Cook and Ryan Thummel), Research to Prevent Blindness (Kresge Eye Institute - Mark Juzych)
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 1771 – F0320. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Ashley Kramer, Justin Carthage, Marla Spain, Katherine Gurdziel, Tiffany A. Cook, Ryan Thummel; A comparative analysis of gene and protein expression in a zebrafish model of chronic photoreceptor degeneration. Invest. Ophthalmol. Vis. Sci. 2022;63(7):1771 – F0320.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Zebrafish are widely utilized to investigate retinal regeneration as they can regenerate photoreceptors (PRs) following acute phototoxic damage. This is mediated by Müller glia (MG), which re-enter the cell cycle to produce retinal progenitors. While this acute model has revealed important MG-dependent regenerative pathways, it may not fully reflect the events underlying human retinopathies, which often follow a chronic pathological timeline. To test this hypothesis, we developed a zebrafish model of chronic low light (CLL) exposure and compared morphological and transcriptomic changes in the CLL damaged retina to our acute light damage model.

Methods : Adult albino zebrafish were exposed to 28 days of CLL and eye tissue was collected at 8 time points. Whole right eyes were collected for immunohistochemistry and whole retinas from the left eyes were used for 3’mRNA-seq.

Results : CLL exposure resulted in the truncation of PR outer segments, and reduced numbers of rod PR nuclei by 28 days post light (dpl) (Fig. 1). Unlike the acute model, MG cell-cycle re-entry was not observed in CLL, suggesting that this damage paradigm is not sufficient to trigger MG-mediated regeneration. Additionally, we did not detect any overt signs of MG gliosis, as is seen early in the acute model. However, we did observe a peak of inflammatory markers (i.e. mpeg1.1, apoeb) by 10dpl, much later than seen in the acute model. This corresponded with a gradual accumulation of microglia at the tips of rod outer segments. Transcriptomic comparisons corresponding to PR differentiation in the acute model vs PR degeneration in the CLL model revealed a set of inversely correlated genes likely representing PR development and maintenance. We detected genes known to be involved in human retinal disease (pdca/b, gnat1/2, grk1a/b, rom1b), and genes not yet characterized in zebrafish regenerative retinal biology (kera, pdca/b).

Conclusions : By comparing the molecular and cellular changes associated with acute vs chronic models of PR degeneration, we identified several candidate genes involved in slow PR degeneration and gliosis. These studies serve as a nexus for future experiments aimed at understanding common retinal degenerative diseases.

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

 

Figure 1. Gradual truncation of rod outer segments (Zpr-3) in the CLL model

Figure 1. Gradual truncation of rod outer segments (Zpr-3) in the CLL model

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×