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Francesca BARONE, Luisa Vera Muscatello, Domenico Ventrella, Alberto Elmi, Luca Laghi, Fabio Benfenati, Grazia Pertile, Maria Laura Bacci; In depth characterization of a pig model of photoreceptor degeneration. Invest. Ophthalmol. Vis. Sci. 2019;60(9):463.
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© ARVO (1962-2015); The Authors (2016-present)
The Iodoacetic acid (IAA) pig model has been suggested as a rapid and cost-effective model of photoreceptor degeneration to test potential drugs and cell therapies. Herein, we present an in-depth characterization of the IAA pig model including functional and morphological description of the optic pathways and vitreous humor (VH) and perform behavioral visual assessment
Commercially obtained pigs were systemically treated with 12 mg/Kg of IAA and analyzed after 30 days. Electrophysiological investigation was performed in 11 treated pigs including full-field electroretinogram ff-ERG, pattern ERG and flash visual evocated potential fVEP; all assessed under general anesthesia (tiletamine-zolazepam 5mg/Kg and sevoflurane). Behavioral vision assessment was performed with an obstacle course test (OC test, 9 treated and 5 untreated) based on the ability of the animals to navigate through ten obstacles, time and number of collisions with obstacles was measured. VH samples were collected from 30 pigs (17 untreated and 13 treated) upon vitrectomy and analyzed by means of 1 H NMR spectroscopy for characterization. Optic tracts (OT), lateral geniculate bodies (LGB) and retinas from 3 treated and 3 untreated pigs were processed and analyzed for histology and immunohistochemistry
The VH characterization validated the metabolic impairment known to be caused by glycolysis inhibition upon IAA treatment. Treated retinas showed a selective atrophy of rods with sparing of cones and decreased cellularity of the outer nuclear layer in the central visual streak. Structural data were confirmed by ff-ERG and fVEP that revealed partially preserved cones and combined response and abolished rod response. Retinal pigmented epithelium, inner nuclear layer, inner plexiform layer, ganglion cells and nerve fibers layers were not affected, but PERG was abolished. Activated microglia, reactive and haphazardly arranged Müller cells were detected in treaded retinas; the astrocytes were increased in the OT while increase of microglia and reduction of oligodendrocytes was observed in LGB. The OC test revealed that pig vision was severely impaired after treatment
12mg/Kg IAA lead to a severe loss of vision due to photoreceptors loss and mild affection of the optic pathways. Our findings will help researchers with a better and more accurate use of IAA pig model for developing potential therapies for retinal degenerative diseases
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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