Cone Photoreceptors Develop Normally in the Absence of Functional Rod Photoreceptors in a Transgenic Swine Model of Retinitis Pigmentosa

Castro, Juan P. Fernandez de; Scott, Patrick A.; Fransen, James W.; Demas, Jay; DeMarco, Paul J.; Kaplan, Henry J.; McCall, Maureen A.

doi:10.1167/iovs.13-13724

Cited by 27 publications

(34 citation statements)

References 43 publications

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“…Our results support the hypothesis that one of the roles of curcumin neuroprotection is to prevent mistrafficking of mutant rhodopsin protein that results in abnormal expression throughout the rod PR. In our previous studies 28,30 we showed that abnormal expression of mutant rhodopsin in P23H miniswine embryos is associated with malformation of rod PR outer segments and spherules, and that P23H piglets never develop rod-driven vision. The amelioration of the morphologic abnormality with curcumin treatment is an important first step because normal rod PRs are a prerequisite to their normal function.…”

Section: Discussionmentioning

confidence: 87%

“…In the Tg P23H rat, where the onset of photoreceptor degeneration is significantly later compared with the Tg pig. 28,30 In addition to curcumin 17 other compounds that produce positive results include: safranal, 36 cannabinoid agonist HU210, 37 tauroursodeoxycholic acid (TUD-CA) 38 proinsulin, 39 Tat-lCL (specific peptide inhibitor of mitochondrial l-calpain), 40 and arimoclomol (heat-shock response coinducer). 41 Neither our study nor the work in the rat have explored the long-term effects of these factors.…”

Section: Discussionmentioning

confidence: 99%

“…28,30 Briefly, a 3-mm wide vertical strip of retinal tissue was removed from the superior retina of the left eye. A 2 3 2 mm piece of retinal tissue was harvested from the vertical band of tissue approximately 5 mm above the superior margin of the optic disc and processed for transmission electron microscopy.…”

Section: Transmission Electron Microscopymentioning

confidence: 99%

“…We sought to determine if curcumin administration would have similar neuroprotective effects in a large animal model of RP, which exhibits functional and morphological characteristics similar to P23H retinopathy in man. 28,29,30 Because alterations in morphology arise prenatally in this swine RP model, we exposed the embryos prenatally to curcumin. Our results show that curcumin delays structural defects in transgenic P23H miniswine embryo rod PRs.…”

Section: Introductionmentioning

confidence: 99%

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Prenatal Exposure to Curcumin Protects Rod Photoreceptors in a Transgenic Pro23His Swine Model of Retinitis Pigmentosa

Scott

Kaplan

McCall

2015

Trans. Vis. Sci. Tech.

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Purpose: Rhodopsin localization and rod photoreceptor (PR) morphology is altered in embryonic transgenic (Tg) Pro23His (P23H) miniswine. At birth, the Tg P23H swine retina lacks rod driven signaling. Curcumin, a neuroprotective food additive, has been shown to rescue Tg P23H rat rod PRs and promote normal trafficking of rhodopsin. We tested the hypothesis that prenatal exposure to curcumin would prevent PR morphological changes in Tg P23H miniswine retinae.Methods: A domestic sow was inseminated with semen from a Tg P23H miniswine founder. Her daily diet was supplemented with curcumin (100 mg/Kg body weight) from embryonic (E) day 80 to E112. The same diet without curcumin was fed to a second inseminated control sow. At E112, 2 days before parturition, both sows were euthanized. Their embryos were harvested, genotyped, and their eyes enucleated and prepared for morphological evaluation.Results: In all pigs, we measured mean outer retinal thickness, localization of rhodopsin, and rod PR morphology. Curcumin-treated Tg P23H swine embryonic retinas were similar to WT. Untreated Tg P23H embryonic retinas show significant degenerative effects; their outer retina was thinner, rod PR morphology was abnormal, and rhodopsin was mislocalized to the outer nuclear layer (ONL).Conclusions: These data support a role for curcumin as a neuroprotective agent that prevents/delays morphological abnormalities associated with rod PR degeneration in this Tg P23H swine model of retinitis pigmentosa (RP).

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Transmission Electron Microscopymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prenatal Exposure to Curcumin Protects Rod Photoreceptors in a Transgenic Pro23His Swine Model of Retinitis Pigmentosa

Scott

Kaplan

McCall

2015

Trans. Vis. Sci. Tech.

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“…Blocks of corneal tissue were cut into 4μm-thick sections using a Leica EMUC6 Ultramicrotome (Leica Microsystems, Buffalo Grove, IL), stained with 1% cresyl violet (Sigma, St. Louis, MO), mounted, and cover-slipped. For TEM, sections were prepared as previously described (Fernandez de Castro et al, 2014; Scott et al ., 2014) and examined with a transmission electron microscope (TEM; Model 300: Phillips, Eindhoven, The Netherlands). Photomicrographs were captured with a digital camera (15 M pixel digital camera, Scientific Instruments and Applications, Duluth, GA) and Maxim DL Version 5 software (Diffraction Limited, Ottawa, Canada).…”

Section: Methodsmentioning

confidence: 99%

Anatomic Studies of the Miniature Swine Cornea

Abhari

Eisenback

Kaplan

et al. 2018

The Anatomical Record

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The domestic swine eye resembles the human eye both anatomically and physiologically. Xenotransplantation of the swine cornea to humans in need of full keratoplasty shows promise as a potential therapeutic strategy to restore vision in individuals with advanced corneal disease, especially those residing in developing nations. That said, we characterized the morphology of corneas from miniature swine, which are smaller in size, easier to handle, and more cost-effective compared to domestic swine. Eyes (N = 15) were harvested from miniature swine from different age groups: 1 month (N = 3), 2 month (N = 3), 4 month (N = 3), 8 month (N = 3), as well as 24 month old adult domestic swine (N = 3). They were immediately submerged in fixative and processed for histological examination at the light and transmission electron microscopic level. Gross anatomic measurements of the cornea were significantly less (P value ≤ 0.05) in miniature swine versus domestic swine. Corneal strata exhibited morphological characteristics similar to the domestic swine cornea. Adult miniature swine corneas show similar overall corneal thickness at 8 months of age versus domestic swine. Miniature swine exhibit similar corneal morphology with the domestic pig and humans, with the exception of Bowman’s layer, which is absent in pigs. Therefore, miniature pigs may be a useful resource of corneal tissue for humans in need of full keratoplasty, as well as serve as a large eye model for ophthalmology residents to develop surgical skills and for development and testing of ocular therapeutic strategies that translate to humans.

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Animal modelling for inherited central vision loss

Kostic

Arsenijévic

2015

The Journal of Pathology

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Disease‐causing variants of a large number of genes trigger inherited retinal degeneration leading to photoreceptor loss. Because cones are essential for daylight and central vision such as reading, mobility, and face recognition, this review focuses on a variety of animal models for cone diseases. The pertinence of using these models to reveal genotype/phenotype correlations and to evaluate new therapeutic strategies is discussed. Interestingly, several large animal models recapitulate human diseases and can serve as a strong base from which to study the biology of disease and to assess the scale‐up of new therapies. Examples of innovative approaches will be presented such as lentiviral‐based transgenesis in pigs and adeno‐associated virus (AAV)‐gene transfer into the monkey eye to investigate the neural circuitry plasticity of the visual system. The models reported herein permit the exploration of common mechanisms that exist between different species and the identification and highlighting of pathways that may be specific to primates, including humans. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

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Cone Photoreceptors Develop Normally in the Absence of Functional Rod Photoreceptors in a Transgenic Swine Model of Retinitis Pigmentosa

Cited by 27 publications

References 43 publications

Prenatal Exposure to Curcumin Protects Rod Photoreceptors in a Transgenic Pro23His Swine Model of Retinitis Pigmentosa

Prenatal Exposure to Curcumin Protects Rod Photoreceptors in a Transgenic Pro23His Swine Model of Retinitis Pigmentosa

Anatomic Studies of the Miniature Swine Cornea

Animal modelling for inherited central vision loss

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