June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Background Data in a Blue Light Model of Retinal Degeneration in the Albino Mouse
Author Affiliations & Notes
  • Kelly Tenneson
    Ocular and Neuroscience, Charles River, Montreal, QC, Canada
  • Mark Vezina
    Ocular and Neuroscience, Charles River, Montreal, QC, Canada
  • Footnotes
    Commercial Relationships Kelly Tenneson, Charles River (E), Eleven Biotherapeutics (E); Mark Vezina, Charles River Laboratories (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 3256. doi:
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      Kelly Tenneson, Mark Vezina; Background Data in a Blue Light Model of Retinal Degeneration in the Albino Mouse. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3256.

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

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Abstract

Purpose: This study was performed to optimize a blue-light model of neurodegeneration.

Methods: BALB/c mice were adapted to ambient light levels of >200 lux during the prestudy period. One subset was given a bilateral intravitreal injection of brain derived neurotrophic factor (BDNF - 1 μg/eye), followed by blue light exposure (460 to 490 nm; ~1100 lux) for 6 or 24 hours, with an undosed control group for each exposure duration. To further investigate the effect of exposure length, an additional subset was dosed unilaterally and exposed to 3 hours of blue light. At the end of a one-week observation period, all animals underwent electroretinography (ERG) and spectral domain optical coherence tomography (SD-OCT) to examine the retinal function and structure in vivo. Eyes were then examined microscopically and retinal outer nuclear layer (ONL) thickness determined by cell count.

Results: Control animals exposed to 6 or 24 hours of blue light demonstrated a significant reduction in retinal function, with ERG response decreased by >90%. This correlated with changes in SD-OCT images consisting of a thinning of the ONL. Microscopic examination confirmed a decrease in the average number of cell layers in the ONL to 1.7 from 11.5, as well as notably reduced cellularity of the retinal ONL and focal deposits of basophilic pigment associated with cellular degeneration and loss. Optimal neuroprotection was offered following bilateral BDNF administration and 6 hours of blue light exposure. Mean ERG response remained comparable, or slightly higher, than baseline (+21%) and no structural changes were seen with OCT or microscopic examination. Other exposure lengths investigated in this study did not show optimal results. BDNF + 24 hours of exposure resulted in a moderately reduced ERG response (-42%), but no structural changes were evident in these animals; 3 hours of exposure was not sufficient to induce measurable retinal damage under these conditions.

Conclusions: In conclusion, retinal damage was effectively induced in albino mice following 6 hours of blue light exposure and the effects monitored using ERG, SD-OCT and histopathology as endpoints. This model was considered suitable to screen new chemical entities (NCE) and investigate their potential for neuroprotection.

Keywords: 615 neuroprotection • 688 retina  
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