X-linked retinitis pigmentosa (XLRP) is a severe, rapidly progressive and incurable retinal degeneration. Molecular genetics research has recently prOvided evidence that there may be heterogeneity within XLRP. These different putative genotypes have shown no clear relation to the phenotypes defined by the only clinical classification scheme of XLRP currently in use. The studies in this proposal aim to provide a new classification scheme of XLRP based on abnormal retinal Mechanisms by examining hemizygotes and heterozygotes with non-invasive retinal function test techniques that have proven valuable in defining the different phenotypes Of autosomal dominant RP. Preliminary electrophysiological and psychophysical studies already indicate there are distinctly different patterns of retinal dysfunction in young XLRP hemizygotes. With full field electroretinography, there are two different relationships of rod- to cone-mediated dysfunction; and with rod and cone perimetry, these two patterns are confirmed and their regional retinal variations defined. Both functional phenotypes in XLRP hemizygotes show unique features when compared to the patterns of dysfunction in well-characterized retinal degenerations such as Types I and II RP and cone-rod dystrophy. Heterozygotes tested with rod and cone perimetry show patches of mild dysfunction with relationships of rod to cone abnormality like those in the hemizygotes. Examples of similar functional patterns in a heterozygote and hemizygote from the same family have been found. The proposed work is to extend these preliminary observations. Hemizygotes will be tested with rod and cone electroretinography, rod and cone perimetry and dark adaptometry to define the patterns of dysfunction and determine if they are consistent within pedigrees. Heterozygotes from the same pedigrees will be tested with rod and cone perimetry and adaptometry and the patterns of dysfunction compared with one another and with those in related hemizygotes to determine if the disease expression in the patchy retinopathy of the heterozygous state is representative of that in the hemizygotes.

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Visual Sciences A Study Section (VISA)
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University of Miami School of Medicine
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