April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Progression of Pro23His Retinopathy in a Miniature Swine Model of Retinitis Pigmentosa
Author Affiliations & Notes
  • Patrick A Scott
    Ophthalmology & Visual Sciences, University of Louisville, Louisville, KY
  • Juan Pablo Fernandez de Castro
    Ophthalmology & Visual Sciences, University of Louisville, Louisville, KY
  • Maureen A McCall
    Ophthalmology & Visual Sciences, University of Louisville, Louisville, KY
  • Henry J Kaplan
    Ophthalmology & Visual Sciences, University of Louisville, Louisville, KY
  • Footnotes
    Commercial Relationships Patrick Scott, None; Juan Fernandez de Castro, None; Maureen McCall, None; Henry Kaplan, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1718. doi:https://doi.org/
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      Patrick A Scott, Juan Pablo Fernandez de Castro, Maureen A McCall, Henry J Kaplan; Progression of Pro23His Retinopathy in a Miniature Swine Model of Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1718. doi: https://doi.org/.

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

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Abstract

Purpose: We have recently generated transgenic P23H (TgP23H) miniature swine founders that exhibit similar characteristics to autosomal dominant retinitis pigmentsosa (RP) in humans. However, morphological changes that occur in retinas in TgP23H swine were not examined until 12 months of age. Here we tracked retinal function and morphology from 1 month to 18 months in F1 progeny of TgP23H miniswine founder 53-1.

Methods: Scotopic (rod-driven) and photopic (cone-driven) retinal function were evaluated in TgP23H and Wt (Wild-type) littermates using full field electroretinograms (ffERGs) at 1, 2, 3, 6, 9, 12, and 18 months of age. Miniswine were euthanized and their retinas processed for morphological evaluation at the light and electron microscopic level.

Results: Wt littermates reached mature scotopic and photopic retinal function by 3 months, while TgP23H miniswine showed abnormal scotopic ffERGs at the earliest time point, 1 month, and depressed photopic ffERGs after 2 months. Rod and cone photoreceptors exhibited morphological abnormalities and dropout from the outer nuclear layer at 1 month, with only a monolayer of cone photoreceptor somata remaining in the outer nuclear layer after 2 months. The retina showed progressive neural remodeling of the outer retina that included dendritic retraction of rod bipolar cells and glial seal formation by Müller cells that was evident by 3 and 9 months, respectively.

Conclusions: TgP23H offspring from miniswine founder 53-1 exhibit functional and morphological features similar to humans with aggressive RP. TgP23H miniature swine are a useful large-eye model to study pathogenesis and preservation of cone photoreceptors in human RP.

Keywords: 696 retinal degenerations: hereditary • 597 microscopy: electron microscopy • 510 electroretinography: non-clinical  
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