Oregon eye disease is an X-linked disorder of retinal function associated with a reduced-amplitude b-wave of the scotopic electroretinogram (ERG). It was described in patients with a contiguous gene deletion syndrome at Xp2l that included the Duchenne muscular dystrophy (DMD) gene. Our data indicate that dystrophin, the product of the DMD gene, is important in the pathogenesis of Oregon eye disease. We propose studies aimed at characterizing the role of dystrophin in retina. We have identified an animal model, the dystrophic mouse mdx(Cv3), with the same electroretinographic abnormalities as seen in Duchenne and Becker muscular dystrophy patients. Human and murine studies suggest that the severity of the ERG findings vary according to the location of the DMD gene defect. Such positional influences may reflect differential expression of dystrophin isoforms in retina. Using immunocytochemistry, we have localized dystrophin to the outer plexiform layer, consistent with the electrophysiologic abnormalities identified. Studies are proposed using Duchenne and Becker muscular dystrophy patients and dystrophic mice that will help elucidate the role of dystrophin in retina.
The specific aims of the study are: I) to examine Duchenne and Becker muscular dystrophy patients and dystrophic mice by electroretinography and correlate the results with the location of DMD gene defects; 2) to perform serial examinations to determine whether the retinal abnormalities are progressive and whether they reflect abnormalities in other CNS tissues; and 3) to characterize the cellular localization of dystrophin in retina and the pattern of dystrophin isoform expression therein. Thus, by defining the role of dystrophin in retina, we hope to contribute to our long term goals of improved understanding of the pathobiology of the retina, the ontogeny of dystrophin expression in retina, the role of dystrophin in Oregon eye disease and allied retinal disorders, and the pattern of dystrophin isoform expression in non-muscle tissues.
