title: Cone photoreceptors develop normally in the absence of functional rod photoreceptors in a transgenic swine model of retinitis pigmentosa.
abstract: OBJECTIVE
  Human and swine retinas have morphological and functional similarities. In the absence of primate models, the swine is an attractive model to study retinal function and disease, with its cone-rich visual streak, our ability to manipulate their genome, and the differences in susceptibility of rod and cone photoreceptors to disease. We characterized the normal development of cone function and its subsequent decline in a P23H rhodopsin transgenic (TgP23H) miniswine model of autosomal dominant RP.
  
  
  METHODS
  Semen from TgP23H miniswine 53-1 inseminated domestic swine and produced TgP23H and Wt hybrid littermates. Retinal function was evaluated using ERGs between postnatal days (P) 14 and 120. Retinal ganglion cell (RGC) responses were recorded to full-field stimuli at several intensities. Retinal morphology was assessed using light and electron microscopy.
  
  
  RESULTS
  Scotopic retinal function matures in Wt pigs up to P60, but never develops in TgP23H pigs. Wt and TgP23H photopic vision matures similarly up to P30 and diverges at P60 where TgP23H cone vision declines. There are fewer TgP23H RGCs with visually evoked responses at all ages and their response to light is compromised. Photoreceptor morphological changes mirror these functional changes.
  
  
  CONCLUSIONS
  Lack of early scotopic function in TgP23H swine suggests it as a model of an aggressive form of RP. In this mammalian model of RP, normal cone function develops independent of rod function. Therefore, its retina represents a system in which therapies to rescue cones can be developed to prolong photopic visual function in RP patients.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky, United States.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Fernandez de Castro
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Scott
authors.forename: James W
authors.initials: JW
authors.lastname: Fransen
authors.forename: James
authors.initials: J
authors.lastname: Demas
authors.forename: Paul J
authors.initials: PJ
authors.lastname: DeMarco
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Kaplan
authors.forename: Maureen A
authors.initials: MA
authors.lastname: McCall
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002452:Cell Count; D004195:Disease Models, Animal; D004596:Electroretinography; D046529:Microscopy, Electron, Transmission; D017949:Retinal Cone Photoreceptor Cells / Q000648:ultrastructure*; D017948:Retinal Rod Photoreceptor Cells / Q000648:ultrastructure*; D012174:Retinitis Pigmentosa / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D012243:Rhodopsin / Q000378:metabolism*; D013552:Swine; D013556:Swine, Miniature
chemical_list: D012243:Rhodopsin
keywords: electron microscopy; electrophysiology; retina; retinitis pigmentosa; swine