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Christian Li, Luis-Fernando Negro Silva, Roy Foster, Simon Authier; WITHDRAWN - Electroretinography evaluation in the Göttingen Minipig: An alternative animal model for ocular preclinical safety assessment. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5532. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The minipig eye shares many similarities to the human eye; making them a suitable large animal model choice in ocular toxicology testing. Electroretinography (ERG) is a common end point used to evaluate retinal toxicity following systemic exposure or ocular administration.
ERGs were recorded using an EPIC-4000 and Ganzfeld dome (LKC Technologies) following unilateral intravitreal injection into the posterior chamber at a dose volume of 100 µL. Gentamicin (5 mg/eye, n=3), indocyanine green (ICG; 0.25 mg/eye, n=4) and glycine (5 mg/eye, n=3) were used as positive controls inducing retinal toxicity, light transmission interference and neurotransmission inhibition, respectively. The contralateral eye served as an untreated control. The ERG protocol included a scotopic luminance-response curve analysis (-4.09 to 0.90 log cds/m2) and oscillatory potentials were assessed at 0.41 log cds/m2. Animals were dark-adapted prior to scotopic assessment. The photopic evaluation included a single flash followed by a 30.3 Hz flicker response at 0.41 log cds/m2. Animals were background light-adapted prior to photopic assessment.
Without pharmacological treatments, scotopic b-wave amplitude and latency recorded in minipigs were comparable to other species including humans. Absolute scotopic a-wave, photopic b-wave amplitudes and oscillatory potentials in minipigs were slightly higher than dogs and rabbits. With 5 mg gentamicin, scotopic b-wave amplitudes were decreased across all light intensities (-1.59 to 0.90 log cds/m2) and with peak effects of -30.2%. Similarly, gentamicin resulted in severely decreased oscillatory potentials (mean reduction of -79.2%). Scotopic a-wave and b-wave amplitudes were generally decreased in eyes treated with 0.25 mg ICG suggesting light transmission interferences. Photopic evaluations revealed a decrease in oscillatory potentials and flicker response in eyes given 5 mg glycine and eyes given 5 mg gentamicin. Log K (retinal sensitivity) was reduced in the eyes given 5 mg gentamicin, but increased in the eyes given 5 mg glycine when compared with the contralateral control eyes.
The results support expected pharmacological effects following intravitreal administration and the ERG protocol evaluated here in minipigs could be considered for the assessment of retinal toxicity in preclinical toxicology studies.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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