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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | McCall, Maureen A. Kaplan, Henry J. Scott, Patrick A. Fernandez de Castro, Juan P. |
| Description | Country affiliation: United States Author Affiliation: Scott PA ( Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky, United States.) |
| Abstract | PURPOSE: Functional studies have detected deficits in retinal signaling in asymptomatic children from families with inherited autosomal dominant retinitis pigmentosa (RP). Whether retinal abnormalities are present earlier during gestation or shortly after birth in a subset of children with autosomal dominant RP is unknown and no appropriate animal RP model possessing visual function at birth has been available to examine this possibility. In a recently developed transgenic P23H (TgP23H) rhodopsin swine model of RP, we tracked changes in pre- and early postnatal retinal morphology, as well as early postnatal retinal function. METHODS: Domestic swine inseminated with semen from a TgP23H miniswine founder produced TgP23H hybrid and wild type (Wt) littermates. Outer retinal morphology was assessed at light and electron microscopic levels between embryonic (E) and postnatal (P) day E85 to P3. Retinal function was evaluated using the full field electroretinogram at P3. RESULTS: Embryonic TgP23H rod photoreceptors are malformed and their rhodopsin expression pattern is abnormal. Consistent with morphological abnormalities, rod-driven function is absent at P3. In contrast, TgP23H and Wt cone photoreceptor morphology (E85-P3) and cone-driven retinal function (P3) are similar. CONCLUSIONS: Prenatal expression of mutant rhodopsin alters the normal morphological and functional development of rod photoreceptors in TgP23H swine embryos. Despite this significant change, cone photoreceptors are unaffected. Human infants with similarly aggressive RP might never have rod vision, although cone vision would be unaffected. Such aggressive forms of RP in preverbal children would require early intervention to delay or prevent functional blindness. |
| ISSN | 01460404 |
| e-ISSN | 15525783 |
| DOI | 10.1167/iovs.13-13723 |
| Journal | Investigative Opthalmology & Visual Science |
| Issue Number | 4 |
| Volume Number | 55 |
| Language | English |
| Publisher | Association for Research in Vision and Ophthalmology |
| Publisher Date | 2014-04-28 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Genetics Mutation Retinal Rod Photoreceptor Cells Metabolism Retinitis Pigmentosa Rhodopsin Biosynthesis Animals Animals, Genetically Modified Dna Mutational Analysis Disease Models, Animal Electroretinography Genotype Immunohistochemistry Microscopy, Electron, Transmission Polymerase Chain Reaction Ultrastructure Pathology Swine Swine, Miniature Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Ophthalmology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Ophthalmology Sensory Systems Cellular and Molecular Neuroscience |
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