Progression of Pro23His Retinopathy in a Miniature Swine Model of Retinitis Pigmentosa.
OBJECTIVE
We characterize the progression of retinopathy in Filial 1 (F1) progeny of a transgenic (Tg) founder miniswine exhibiting severe Pro23His (P23H) retinopathy.


METHODS
The F1 TgP23H miniswine progeny were created by crossing TgP23H founder miniswine 53-1 with wild type (WT) inbred miniature swine. Scotopic (rod-driven) and photopic (cone-driven) retinal functions were evaluated in F1 TgP23H and WT littermates using full field electroretinograms (ffERGs) at 1, 2, 3, 6, 9, 12, and 18 months of age, as well as the Tg founder miniswine at 6 years of age. Miniswine were euthanized and their retinas processed for morphologic evaluation at the light and electron microscopic level. Retinal morphology of a 36-month-old Tg miniswine also was examined.


RESULTS
Wild type 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 (PR) exhibited morphologic abnormalities and dropout from the outer nuclear layer at 1 month, with only a monolayer of cone PR somata remaining after 2 months. The retinas showed progressive neural remodeling of the outer retina that included dendritic retraction of rod bipolar cells and glial seal formation by Müller cells. The TgP23H founder miniswine showed cone PR with relatively intact morphology exclusive to the area centralis.


CONCLUSIONS
The F1 Tg miniswine and the TgP23H founder miniswine exhibit similar retinopathy.


CONCLUSIONS
TgP23H miniswine are a useful large-eye model to study pathogenesis and preservation cone PRs in humans with retinitis pigmentosa.
Department of Ophthalmology & Visual Sciences, University of Louisville, Louisville, KY, USA ; Department of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, KY, USA.
Patrick A
PA
Scott
Department of Ophthalmology & Visual Sciences, University of Louisville, Louisville, KY, USA.
Juan P Fernandez
JP
de Castro
Department of Ophthalmology & Visual Sciences, University of Louisville, Louisville, KY, USA ; Department of Psychological and Brain Sciences, University of Louisville, Louisville, KY, USA.
Paul J
PJ
DeMarco
Department of Animal Science, Iowa State University, Ames, IA, USA.
Jason W
JW
Ross
Department of Animal Science, Iowa State University, Ames, IA, USA.
Josephat
J
Njoka
Division of Animal Science, University of Missouri-Columbia, Columbia, MO, USA ; Department of National Swine Resource and Research Center, University of Missouri-Columbia, Columbia, MO, USA.
Eric
E
Walters
Division of Animal Science, University of Missouri-Columbia, Columbia, MO, USA ; Department of National Swine Resource and Research Center, University of Missouri-Columbia, Columbia, MO, USA.
Randall S
RS
Prather
Department of Ophthalmology & Visual Sciences, University of Louisville, Louisville, KY, USA ; Department of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, KY, USA.
Maureen A
MA
McCall
Department of Ophthalmology & Visual Sciences, University of Louisville, Louisville, KY, USA ; Department of Microbiology and Immunology, University of Louisville, Louisville, KY, USA.
Henry J
HJ
Kaplan
retinal degeneration; retinitis pigmentosa; swine