Rapid Recovery of Visual Function Associated with Blue Cone Ablation in Zebrafish

PLoS One. 2016 Nov 28;11(11):e0166932. doi: 10.1371/journal.pone.0166932. eCollection 2016.

Abstract

Hurdles in the treatment of retinal degeneration include managing the functional rewiring of surviving photoreceptors and integration of any newly added cells into the remaining second-order retinal neurons. Zebrafish are the premier genetic model for such questions, and we present two new transgenic lines allowing us to contrast vision loss and recovery following conditional ablation of specific cone types: UV or blue cones. The ablation of each cone type proved to be thorough (killing 80% of cells in each intended cone class), specific, and cell-autonomous. We assessed the loss and recovery of vision in larvae via the optomotor behavioural response (OMR). This visually mediated behaviour decreased to about 5% or 20% of control levels following ablation of UV or blue cones, respectively (P<0.05). We further assessed ocular photoreception by measuring the effects of UV light on body pigmentation, and observed that photoreceptor deficits and recovery occurred (p<0.01) with a timeline coincident to the OMR results. This corroborated and extended previous conclusions that UV cones are required photoreceptors for modulating body pigmentation, addressing assumptions that were unavoidable in previous experiments. Functional vision recovery following UV cone ablation was robust, as measured by both assays, returning to control levels within four days. In contrast, robust functional recovery following blue cone ablation was unexpectedly rapid, returning to normal levels within 24 hours after ablation. Ablation of cones led to increased proliferation in the retina, though the rapid recovery of vision following blue cone ablation was demonstrated to not be mediated by blue cone regeneration. Thus rapid visual recovery occurs following ablation of some, but not all, cone subtypes, suggesting an opportunity to contrast and dissect the sources and mechanisms of outer retinal recovery during cone photoreceptor death and regeneration.

MeSH terms

  • Ablation Techniques
  • Animals
  • Animals, Genetically Modified
  • Cell Death
  • Cell Proliferation
  • Larva
  • Melanins / metabolism
  • Metronidazole / pharmacology
  • Nitroreductases / genetics
  • Nitroreductases / metabolism
  • Pigmentation
  • Retina / cytology
  • Retinal Cone Photoreceptor Cells / drug effects
  • Retinal Cone Photoreceptor Cells / physiology*
  • Retinal Degeneration
  • Ultraviolet Rays
  • Vision, Ocular / physiology*
  • Zebrafish / genetics*

Substances

  • Melanins
  • Metronidazole
  • Nitroreductases

Grants and funding

NCLN was supported by the University of Alberta Undergraduate Research Initiative (http://www.uri.ualberta.ca). MGD was supported by MD/PhD Studentships from the Canadian Institutes of Health Research (http://www.cihr-irsc.gc.ca) and from Alberta Innovates Health Solutions. SYC was funded by Studentships from Alberta Innovates Health Solutions (http://www.aihealthsolutions.ca) and NSERC. APO was supported by a CGSM Studentship from NSERC. Research was funded by Operating grants from the Natural Sciences and Engineering Research Council of Canada (NSERC http://www.nserc-crsng.gc.ca) to WTA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.