Progression of Pro23His Retinopathy in a Miniature Swine Model of Retinitis Pigmentosa.

Purpose: We characterize the progression of retinopathy in Filial 1 (F1) progeny of a transgenic (Tg) founder miniswine exhibiting severe Pro23His (P23H) retinopathy.

Methods: The F1 TgP23H miniswine progeny were created by crossing TgP23H founder miniswine 53-1 with wild type (WT) inbred miniature swine. Scotopic (rod-driven) and photopic (cone-driven) retinal functions were evaluated in F1 TgP23H and WT littermates using full field electroretinograms (ffERGs) at 1, 2, 3, 6, 9, 12, and 18 months of age, as well as the Tg founder miniswine at 6 years of age.

Orbital cellulitis and corneal ulcer due to Cedecea: First reported case and review of the literature.

Cedecea is a gram-negative bacterium from the family Enterobacteriaceae, rarely associated with human infection. We report the first case of an orbital cellulitis and corneal ulcer due to Cedecea in a patient who sustained a motor vehicle accident and was then found to have a retained wooden orbital foreign body.

Role of retinal pigment epithelial cell β-catenin signaling in experimental proliferative vitreoretinopathy.

Proliferative vitreoretinopathy is caused by the contraction of fibrotic membranes on the epiretinal surface of the neurosensory retina, resulting in a traction retinal detachment and loss of visual acuity. Retinal pigment epithelial (RPE) cells play an important role in formation of such fibrotic, contractile membranes. We investigated the role of Wnt/β-catenin signaling, a pathway implicated in several fibrotic diseases, in RPE cells in proliferative vitreoretinopathy.

Cone photoreceptors develop normally in the absence of functional rod photoreceptors in a transgenic swine model of retinitis pigmentosa.

Purpose: 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.

A Pro23His mutation alters prenatal rod photoreceptor morphology in a transgenic swine model of retinitis pigmentosa.

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.

Inhibition of PVR with a tyrosine kinase inhibitor, dasatinib, in the swine.

Purpose: We tested the efficacy of dasatinib, a Food and Drug Administration (FDA)-approved tyrosine kinase inhibitor, to prevent proliferative vitreoretinopathy (PVR).

Methods: The effect of dasatinib on RPE sheet growth was determined by measuring enlargement of cultured RPE sheets in the presence or absence of dasatinib. Epithelial-mesenchymal transition (EMT) of RPE cells was assessed by expression of S100A4.

Iodoacetic acid, but not sodium iodate, creates an inducible swine model of photoreceptor damage.

Our purpose was to find a method to create a large animal model of inducible photoreceptor damage. To this end, we tested in domestic swine the efficacy of two chemical toxins, known to create photoreceptor damage in other species: Iodoacetic Acid (IAA) and Sodium Iodate (NaIO(3)). Intravenous (IV) administration of NaIO(3) up to 90 mg/kg had no effect on retinal function and 110 mg/kg was lethal.

Generation of an inbred miniature pig model of retinitis pigmentosa.

Purpose: The Pro23His (P23H) rhodopsin (RHO) mutation underlies the most common form of human autosomal dominant retinitis pigmentosa (adRP). The objective of this investigation was to establish a transgenic miniature swine model of RP using the human P23H RHO gene.

Methods: Somatic cell nuclear transfer (SCNT) was used to create transgenic miniature pigs that expressed the human P23H RHO mutation.