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Wankun Xie, Min Zhao, Shu-Huai Tsai, Travis W Hein, Lih Kuo, Robert H Rosa; Progression of photoreceptor degeneration in a porcine model of retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. 2017;58(8):274.
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© ARVO (1962-2015); The Authors (2016-present)
Retinitis pigmentosa (RP) is a group of inherited diseases that cause severe visual dysfunction due to progressive degeneration of the photoreceptors. A Pro23His rhodopsin transgenic (TgP23H) pig model of RP was recently developed; however, the information on the temporal correlation between functional/morphological changes and alterations in photoreceptor gene expression remains limited. Herein, we tracked the changes in retinal function and in vivo and ex vivo morphology, and then correlated function-histology with photoreceptor gene expression at various timepoints after birth in TgP23H pigs.
TgP23H and wild type (Wt) hybrid pig littermates were obtained from the National Swine Resource and Research Center. Full-field electroretinography (ERG) and spectral domain optical coherence tomography (SD-OCT) were used to evaluate the retinal function and in vivo retinal morphology, respectively, every 15 days between postnatal days (P) 30 and 120. Retinal histology was evaluated by light microscopy of plastic-embedded sections and the photoreceptor-specific gene expression in the retinal tissue was assessed by real time RT-PCR. Retinal function, morphology, and photoreceptor gene expression were correlated with time.
In TgP23H pigs, the mean a- and b-wave amplitudes at a stimulus intensity of 3.0 cd●s●m-2 were not altered before P45; however, both amplitudes decreased by approximately 70% under photopic and scotopic conditions between P45 and P120. SD-OCT and light microscopy revealed a significant decrease in outer nuclear layer (ONL) thickness by 80% and 70%, respectively, between P45 and P120. The number of photoreceptor nuclei in the ONL measured by light microscopy was significantly decreased by 75% between P45 and P120. The mRNA expression of rhodopsin, recoverin, phosducin, and neural retinal leucine zipper reached a peak level at P60 and rapidly decreased by 90%, 76%, 57% and 96%, respectively, between P60 and P120.
In this study, we longitudinally characterized the progression of photoreceptor degeneration using functional, morphological, and molecular assays in a large animal model of inherited retinal degeneration. The photoreceptors degenerate at a fast rate between P45 and P120 in the TgP23H pig, as measured by ERG, SD-OCT, and histology. The reduction in photoreceptor-specific gene expression appeared to lag behind the ERG and morphologic alterations until after P60.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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