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N. W. Khan, G. Grahek, H. Khanna, J. R. Heckenlively; Natural History and Characterization of a Mouse Model (rd9) of X-Linked Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4068.
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© ARVO (1962-2015); The Authors (2016-present)
To assess the natural history of degeneration by characterizing detailed electrophysiological analysis of age-dependent photoreceptor dysfunction in the rd9 mouse as a model of X-linked RP.
Male rd9 mice, and age-matched C57BL/6 control mice were studied at 1 to 24 months by standardized electroretinograms (ERG), a-wave phototransduction modeling, and correlative retinal histology. ERG results were compared at different ages with a previously reported model of XLRP, the Rpgr KO mouse1 (LKO).
Scotopic ERG a- and b-wave and the photopic light-adapted b-wave amplitudes of the rd9 mice were comparable to those of wild type C57 mice at 1 month. There was a sharp amplitude decline of 40% in the scotopic a- and b-waves from 1 to 4 months age, followed by minimal change in ERG amplitudes from 4 to 12 months. Amplitudes decreased steadily with age after 12 months. The photopic b-wave was reduced by 30% from 1 to 4 months, and mirrored the slow degeneration phase of the scotopic ERG from 4 to 12 months. Rod b-wave maximum amplitude, Vmax and response sensitivity k, determined by fitting the Naka-Rushton equation to the scotopic b-wave showed a 40% reduction in Vmax and no significant change in k from control. A-wave thresholds increased by 0.6 log units and b-wave thresholds increased by 0.5 log units from 1 to 4 months, but remained stable until 16 months. Phototransduction sensitivity was in the normal range up to 16 months. B:A-wave ratio consistently stayed above normal mean from 1 to 16 months. Although the ERG amplitude decreased with age, waveform morphology was intact. Inner retinal function was assessed by the amplitude of the photopic negative response (PhNR) and the sum of the amplitudes of the first six oscillatory potentials (OPs). By 16 months the scotopic and photopic ERG amplitudes were reduced by 50%, the PhNR was reduced by 30%, and the OPs by 40%. Histology showed progressive rod outer segment and outer nuclear layer thinning. Rod and cone function progressed much more rapidly in the LKO mouse and were reduced by more than 50% by 6 months.
The ERG shows that the rd9 mouse manifests two stages of degeneration; the first is early and rapid from 1 to 4 months, and the second is late and gradual. The ERG shows a slowly progressive rod and cone dysfunction with better preservation of the inner retina.1. Hong, D.H. et al., PNAS. 2000; 97: 3649-54.
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