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J. Carroll, R. C. Baraas, J. I. W. Morgan, D. R. Williams, D. H. Foster, M. Neitz; Expression of C203R Mutant Cone Pigment Results in Cone Degeneration. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3814.
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© ARVO (1962-2015); The Authors (2016-present)
Nearly all mutations in human rhodopsin result in autosomal dominant retinitis pigmentosa, a disease characterized by rod cell death and secondary cone degeneration. One such mutation (substitution of Tyrosine for Cysteine at position 187) disrupts a disulfide bond that is essential for the proper folding of the photopigment. The analogous mutation in the human L/M cone pigment (substitution of Arginine for Cysteine at position 203) has been associated with red/green color vision defects and blue cone monochromacy. The aim of this work was to determine the effect of expressing this mutant pigment on cone viability.
An adaptive-optics ophthalmoscope was used to image the cone mosaic of 2 unrelated males (AO4511 & AO4515), each having a C203R mutation in one of the genes of their L/M array. The position of the gene carrying the C203R mutation was determined by long-range PCR and DNA sequencing. Real-time quantitative PCR was used to estimate the number of genes per array. Autofluorescence imaging with an AO-SLO was used to measure RPE cell density in the peripheral retina, and OCT images were obtained with the Stratus OCT to assess retinal thickness.
Each individual had three M genes in his array; in AO4515 the C203R mutation was in the 2nd gene of the array whereas in AO4511 the mutation was in the 3rd gene. Both individuals showed signs of cone degeneration; their cone mosaics had significantly decreased density and regularity compared to normal controls. Mid-peripheral RPE cell density was consistent with previously obtained values from histology, suggesting that the cone loss did not affect the viability of the RPE. OCT images revealed macular thinning in AO4515, but not AO4511, whereas fundus examination revealed subtle foveal granularity in both individuals. Visual acuity was normal in both individuals.
The results suggest that whether in rod or cone, expression of this mutant pigment results in cell death. Differences between the appearance of the C203R mosaic and mosaics associated with other disruptions in cone-pigment expression suggest differences in the onset of degeneration. In addition, the results for A04511 are consistent with the hypothesis that the 3rd gene in the array can be expressed in a significant subset of cone photoreceptors.
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