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Patrick Scott, Henry Kaplan; Transmission Electron Microscopic Study of P23H Retinopathy in a Swine Model of Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2013;54(15):645.
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© ARVO (1962-2015); The Authors (2016-present)
Characterize ultrastructural changes that occur during retinogenesis and postnatal development in transgenic (tg) swine expressing the Proline-23-Histidine (P23H) rhodopsin mutation, the most common form autosomal dominant Retinitis Pigmentosa (adRP) in man, which are not detectable with standard histology and immunohistochemistry.
P23H and wild type (Wt) swine were euthanized during gestation at embryonic (E) day 85, 105, and after birth at postnatal (P) days 3, 14, 30, 60, 90, 120, and 180. Each group contained 1 Wt and 1 tg eye (N = 18 eyes). Eyes were fixed in a mixture of 2% paraformaldehyde/2% glutaraldehyde. Posterior eyecups containing the retina were bisected along the vertical meridian and retinal tissue was retrieved 5-7 mm above the optic disc and processed for transmission electron microscopy (TEM).
Wt: E85 retinae exhibit photoreceptor (PR) inner segments (IS) in the subretinal space (SRS) and no PR synaptic terminals in the OPL. E105 retinae show PR outer segments (OS) in the SRS, and development of PR synaptic terminals is incomplete. P3-P180 Wt retinae appear mature and normal. P23H: E85 retinae look similar to Wt. E105 retinae exhibit abnormal rod OS that are disorganized, vacuolated, and truncated; PR synaptic terminals appear similar to Wt. P3 retinae exhibit rod inner segments (IS) with malformed OS, rod spherules have abnormal triad configuration, or no triads at all, and most cones appear normal. P14-P60 retinae show no rod IS/OS, abnormal rod spherules, progressive loss of PR nuclei from the ONL, infrequent pyknotic nuclei in the ONL, Müller cell hypertrophy, cone PRs with and without OS, and flattening of cone pedicles. P90 -P120 retinae show few cone OS, blob-like structures and vacuoles in the cone myoid, and vacuoles in the ONL, INL, and OPL. P180 show abnormal and normal cone somata with retracted abnormal pedicles surrounded by Müller cell cytoplasm, cone IS are largely absent, and the retinal pigment epithelium abuts the external limiting membrane.
P23H tg swine exhibit progressive retinopathy that begins before birth and has a primary effect on rod PRs, followed by a secondary protracted phase of cone PR degeneration. This may be a useful model for studying the protracted phase of cone PR degeneration, and for development of intervention therapies intended to preserve vision in humans with RP.
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