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E. Strettoi, E. Terzibasi, A. Asta, C. Gargini; Retinal Organization in the rd10 Mutant Mouse: A Morphological and ERG Study . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5242.
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Purpose: Retinal degeneration 10 (rd10) mice are a valuable model of autosomal recessive Retinitis Pigmentosa, first described by Chang et al. in 2002. These mice carry a spontaneous re–mutation of the rod–phosphodiesterase (PDE) gene, producing a missense encoding sequence. In the resulting phenotype, a centre–to–periphery rod degeneration starts around P18. Later, cones are lost as well. Aim of this study is to provide a comprehensive analysis of the morphology and function of the rd10 mouse retina during the time span of maximum photoreceptor degeneration, with special attention to the preservation of inner neurons. Methods: Immunocytochemistry with cell type–specific antibodies and confocal microscopy were used to study the morphology of retinal cells in rd10 and C57Bl6J control mice, aged 10–60 days. Photoreceptors, rod and cone bipolar cells, horizontal cells and several types of amacrine cells were studied. Single cells were labeled by gene–gun fluorescent staining. ERG recordings were obtained between P18 and P30 with standard techniques, in response to both flashes and light stimuli sinusoidally modulated in time. Results:Photoreceptor degeneration in the rd10 retina peaks between 20 and 30 days. Tunel staining suggests photoreceptor apoptosis. At P20, rod bipolar cells have normal morphology and a regular complement of mGluR6 receptors. At P30, when many rods have degenerated, rod bipolar dendrites have largely retracted; mGluR6 immunoreactivity has decreased and misplaced in the INL. Other cell types appear well preserved throughout the period of photoreceptor degeneration. The analysis of the leading edge of the a–wave of the ERG (Lamb & Pugh, 1992) shows a reduction of the amplification factor as expected from the underlying PDE mutation. The attenuation characteristics obtained from sinusoidally modulated stimuli reveal a response suppression in the frequency range of 2–10 Hz. This observation is consistent with a reduced band amplification by bipolar cells. Conclusions: As in other models of photoreceptor degeneration, rod bipolar cells of the rd10 retina undergo dendritic retraction at late stages of photoreceptor degeneration; compared to the more aggressive rd1 mutation, the inner retina of rd10 mice is more preserved. ERG recordings reveal alterations in the physiology of the inner retina as early as P18, when morphological changes of inner cells are minimal. A decrease in the content of mGluR6, later detected by immunocytochemistry, could explain this functional decay.
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