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W.A. Beltran, G.M. Acland, G.D. Aguirre; Morphologic Analysis of Clonal Retinal Disease in Carriers of RPGRORF15 Frameshift Mutation . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2069.
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© ARVO (1962-2015); The Authors (2016-present)
To characterize the time course of retinal disease in carriers of XLPRA2, a canine model of early onset XLRP caused by a 2 nucleotide deletion in RPGRORF15 that results in a gain of function from a shift in the reading frame.
Retinas from 9 female carriers dogs (ages: 3.9 weeks–39 weeks) were examined. The tissues were fixed and embedded either in epoxy resin or in OCT medium. Cytologic characteristics of the disease were examined on semithin plastic sections, and by immunohistochemistry on cryosections using a battery of cell–specific antibodies. The course of cell death was monitored by TUNEL assay.
Numerous focal patches of photoreceptor (PR) degeneration were recognizable as early as 4.9 weeks of age. These showed disorganization of their outer segments, increase in ONL thickness, and rod and cone opsin mislocalization. The proportion of TUNEL–positive PRs peaked at 5.9 weeks of age, and was significantly reduced after 12 weeks. By 7.9 weeks of age, patchy remodeling of the inner retina, such as retraction of rod bipolar cell dendrites and increased Müller cell GFAP reactivity was associated with the foci of rod degeneration. In older animals (24–39 weeks) despite a thinning of the ONL, the overall morphology of the remaining OS, IS, ONL and INL was better than in younger dogs. At these ages, patches of rod degeneration were rare but clumps of cone somatas could be seen.
Carrier females of XLPRA2 show an early and severe multifocal retinal degeneration consistent with random X–chromosome inactivation. In older animals there was a generalized reduction in ONL thickness with rare small foci of degeneration persisting.
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