April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Zebrafish as a Model to Study Emmetropization, Refractive Error, and Retinal Substructure using Spectral Domain-Optical Coherence Tomography
Author Affiliations & Notes
  • Ross F Collery
    Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI
  • Francie Moehring
    Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI
  • Robert F Cooper
    Biomedical Engineering, Marquette University, Milwaukee, WI
  • Adam M Dubis
    Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI
  • Joseph Carroll
    Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI
    Ophthalmology, Medical College of Wisconsin, Milwaukee, WI
  • Brian A Link
    Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI
  • Footnotes
    Commercial Relationships Ross Collery, None; Francie Moehring, None; Robert Cooper, None; Adam Dubis, None; Joseph Carroll, None; Brian Link, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 3035. doi:https://doi.org/
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      Ross F Collery, Francie Moehring, Robert F Cooper, Adam M Dubis, Joseph Carroll, Brian A Link; Zebrafish as a Model to Study Emmetropization, Refractive Error, and Retinal Substructure using Spectral Domain-Optical Coherence Tomography. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3035. doi: https://doi.org/.

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

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Abstract
 
Purpose
 

Spectral-domain optical coherence tomography (SD-OCT) accurately measures the anatomy and dimensions of the eye in vivo. Here, we characterize emmetropization of wild-type zebrafish, myopia onset in bugeye/lrp2 mutants, and visualize the highly ordered cone photoreceptor mosaic by SD-OCT. We combine high resolution visualization with an animal model amenable to genetic manipulation that can be used to study candidate genes for refractive error and other ocular diseases.

 
Methods
 

Eye axial length, focal length and lens diameter were measured in wild-type and bugeye/lrp2 mutant zebrafish throughout their lifespan using a Bioptigen SD-OCT system. Cone photoreceptor mosaics were visualized using en face summed volume projection (SVP) images derived from the SD-OCT volume scans. Melanin synthesis was ablated in a subset of RPE cells using TALEN-mediated inactivation of tyrosinase.

 
Results
 

We found that wild-type zebrafish became emmetropic by 1 month, while bugeye/lrp2 mutants were myopic, and worsened as they aged. Wild-type fish maintained emmetropia, and our data show that their lenses grow to balance the focusing power required as eye size increases. By generating SVP images at different retinal depths, we visualized the UV and S cone submosaics. Density measurements of these submosaics agreed with published values from histology. SVP images focused on the RPE layer showed regional melanin inhibition provided by the TALEN technique, with improved discrimination of the cone-RPE interface and underlying choroid and sclera in B-scans of 'windows' of non-pigmented RPE.

 
Conclusions
 

As the zebrafish eye uses only lens refraction and axial length to control emmetropia, we can assay the effects of genes associated with myopia specifically on axial length modulation, the largest single contributor to refractive error. Changes in retinal morphology can be assessed during induction of blinding disorders by SD-OCT, and changes in cone density or patterning can be used to assess photoreceptor damage in visual disorders.

 
 
A. B-scan showing anatomy of adult zebrafish eye; B. B-scan of adult zebrafish retina; C. en face (SVP) showing photoreceptor mosaic; D. merged SVPs from different depths showing UV cone and S cone submosaics (magenta, green); E. SVP of mosaic RPE showing non-pigmented cell areas (dark) surrounded by normal pigmented areas (bright)
 
A. B-scan showing anatomy of adult zebrafish eye; B. B-scan of adult zebrafish retina; C. en face (SVP) showing photoreceptor mosaic; D. merged SVPs from different depths showing UV cone and S cone submosaics (magenta, green); E. SVP of mosaic RPE showing non-pigmented cell areas (dark) surrounded by normal pigmented areas (bright)
 
Keywords: 605 myopia • 552 imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound)  
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