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Doug Emery, Ilya Chernyavskiy, Henry Kaplan, Patrick Scott; Photoreceptor Degeneration and Retinal Remodeling in P23H Transgenic Swine. Invest. Ophthalmol. Vis. Sci. 2013;54(15):713.
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Morphological characterization of photoreceptor degeneration and retinal remodeling in transgenic hybrid swine expressing the Proline-23-Histidine (P23H) rhodopsin mutation, the most common form autosomal dominant Retinitis Pigmentosa (adRP) in man. We investigated whether progressive loss of photoreceptors is accompanied by retinal remodeling in P23H transgenic hybrid swine.
P23H transgenic hybrid swine and age-matched wild type (Wt) controls were euthanized at postnatal (P) day 14, 30, 60, 90, and 120. Each group contained ≥ 2 wt eyes and ≥ 2 transgenic eyes (N = 27 eyes). Eyes were enucleated and fixed in 4% paraformaldehyde in PO4 buffer. Posterior eyecups containing the retina were bisected along the vertical and horizontal meridians and processed for standard histology and immunohistochemistry. Photoreceptor degeneration was quantified at specific locations along the vertical and horizontal meridian, extending from the optic disc to the termination of the peripheral retina. Retinae were also examined for TUNEL-positive cells in the outer and inner retinal layers. Specific cell populations in the inner and outer retinae were labeled with anti-bodies to look for evidence of retinal remodeling.
P23H retinae exhibited significant reductions in the mean number of rows of nuclei in the outer nuclear layer (ONL) from P14-P120, and the spatial distribution of photoreceptor degeneration transitioned from a central-to-peripheral pattern to a more uniform pattern, leaving only a mono-layer of cone somata at P90-P120. TUNEL-positive cells were found scattered throughout the ONL from P14-P30, with only a few TUNEL-positive cells in P60-P120. P23H retinae exhibited a progressive decrease in rhodopsin immunoreactivity, as well as mistrafficking of rhodopsin to the ONL. No dendritic retraction or neuritic sprouting of horizontal or rod bipolar cells was detected. Glial fibrillary acidic protein (GFAP) immunoreactivity was increased in P23H retinae and was most intense at P14 and P120.
P23H transgenic hybrid swine exhibit relatively mild retinal remodeling despite robust loss of rod photoreceptors. This may be a useful model for development of intervention therapies that require a relatively intact inner retina, as well as determine which therapies that may best translate to man.
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