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Patrick A. Scott, Wei Wang, Jason W. Ross, Henry J. Kaplan; Anatomical Evidence of Photoreceptor Degeneration in P23H Mutant Rhodopsin Transgenic Hybrid Swine. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2576.
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Retinitis pigmentosa (RP) is an inherited retinal degeneration that causes progressive loss of rod photoreceptors (PR), affecting cones later in the disease. While rodent models of retinal degeneration have bettered our understanding of inherited retinal disease, differences in eye size, retinal anatomy and physiology, render many of these models ill-suited for studying retinal intervention therapies intended for man. Because the swine eye closely resembles the human eye, our group has created transgenic hybrid swine with the most common autosomal dominant rhodopsin mutation, Proline-23-Histidine (P23H). We investigated whether the P23H rhodopsin mutation induces PR degeneration in swine eyes, as well as the progression and topographical distribution of PR degeneration in the P23H transgenic hybrid swine.
P23H swine and age-matched wild type (wt) controls were euthanized at post-natal days (D) 3, 14, 25, 30, 60, 90, and 120. Eyes were enucleated and fixed in 4% paraformaldehyde in PO4 buffer. Each group contained 1 wt eye and at least 1 transgenic eye. Posterior eyecups containing the retina were bisected along the vertical and horizontal meridians and processed for light microscopy. To quantify PR degeneration, rows of nuclei in the outer nuclear layer (ONL) and inner nuclear layer (INL) were counted at specific locations along the vertical and horizontal meridian.
With the exception of D3, significant reductions in the mean number of rows of nuclei in the ONL were found in all P23H pigs, and ONL reduction appears to be related temporally. D90 and D120 P23H pigs were most severely affected, with only a single row of nuclei remaining in the ONL. The INL was minimally disturbed, with small but significant increases in the number of nuclei in D90 and D120 P23H pigs, as compared to wt.
P23H transgenic hybrid swine exhibit morphological changes to rod photoreceptors that are evident shortly after birth, followed by progressive dropout of rods across the retina. This may be a useful model for development of intervention therapies that can eventually be applied to humans with PR degeneration.
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