June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
Transcriptional changes in photoreceptor development genes during regeneration after cone ablation in zebrafish
Author Affiliations & Notes
  • A Phil Oel
    Biological Sciences, University of Alberta, Edmonton, AB, Canada
  • Michele DuVal
    Biological Sciences, University of Alberta, Edmonton, AB, Canada
  • W Ted Allison
    Biological Sciences, University of Alberta, Edmonton, AB, Canada
  • Footnotes
    Commercial Relationships A Oel, None; Michele DuVal, None; W Allison, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 452. doi:
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      A Phil Oel, Michele DuVal, W Ted Allison; Transcriptional changes in photoreceptor development genes during regeneration after cone ablation in zebrafish. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):452.

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

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Purpose: Genes controlling differentiation of developing photoreceptors have been identified in mouse and zebrafish; however, regulation of the teleost ability to robustly regenerate lost photoreceptors remains uncharacterized. We hypothesize that this regeneration recapitulates development; here, we test whether developmentally important genes are transcriptionally active during the regeneration period of post-injury neural retinas isolated from adult zebrafish.

Methods: We induced regeneration in adult zebrafish in two ways: intense light exposure causing widespread photoreceptor death, and conditional genetic ablation of either UV or blue light-sensitive cones. Conditional genetic ablation of cones occurs when the pro-drug metronidazole (MTZ) is added to tank water of transgenic fish expressing bacterial nitroreductase (NTR) in either UV or blue cones; cells expressing NTR convert MTZ into a DNA-crosslinking agent, causing cell-autonomous apoptosis. After injury by light exposure or MTZ treatment, we isolated the total RNA from neural retinas, and examined the transcriptional activity of several photoreceptor differentiation genes over a time-course by quantitative PCR analysis.

Results: Through light-based ablation we have found changes in expression among rx1, nr2e3, nrl, and thrβ2. Compared to uninjured controls, light blasted retinas show a 2-fold reduction in rx1 transcripts, starting 12hours post ablation (hpa) and lasting until the end of the experiment (96hpa). Expression of nr2e3 is reduced 4-fold and nrl nearly 2-fold over the same period, whereas thrβ2 trends toward increased expression. Transgenic fish exposed to MTZ respond as predicted, showing a loss of NTR-expressing photoreceptors within 15 hours and regenerating new NTR-expressing photoreceptors within a week of recovery after transient treatment with MTZ, with qPCR studies pending.

Conclusions: We examined gene activity during regeneration after either widespread or targeted photoreceptor death. This allows us to evaluate how closely regeneration recapitulates development; to identify genes critical to the regeneration of cone photoreceptors; and finally, to use transgenic tools to modify the endogenous retinal stem cell population, to modulate the outcome of regeneration. This has implications for the design of stem cell-based treatments for blindness, where the restoration of cone-mediated sight is a paramount goal.


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