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J. N. Brodfuehrer, D. C. Dean, P. J. Demarco, L. M. Franco, M. A. McCall, J. H. Sandell, W. Wang, H. J. Kaplan; IAA Creates an Inducible Model of Retinal Degeneration in Swine. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3622.
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© ARVO (1962-2015); The Authors (2016-present)
To create an inducible large animal model of retinal degeneration, we tested the efficacy of two toxins in swine: Iodoacetic Acid (IAA) and Sodium Iodate (NaIO3).
All experiments were conducted in compliance with ARVO statement for the use of animals in Ophthalmic and Vision Research. Retinal function of (n = 55) normal domestic swine were evaluated using functional and clinical tests including: full field electroretinograms (ffERG), indirect ophthalmoscopy, slit lamp, color fundus photography, and fluorescent angiography. At the time of baseline assessment, pigs were administered one of a range of doses of either IAA (n = 32) or NaIO3 (n = 23) intravenously (5 - 30 and 10 - 110 mg/kg, respectively). Changes in retinal function were then evaluated two and five weeks post injection (PI). The pigs were then sacrificed and their eyes were enucleated, and their retinas fixed and prepared for histological evaluation at the light microscopic level.
None of the doses of NaIO3 up to 90 mg/kg have an effect on retinal function and 110 mg/kg is lethal in the pig. 30 mg/kg IAA is a lethal dose in the pig (n = 2) and 5 mg/kg has no obvious effect on retinal structure or function (n = 3). IAA doses of 7.5, 10, and 12 mg/kg (n = 9, 9, 8; respectively) yield a dose response of both structural and functional damage. All three doses significantly reduce ffERG b-wave amplitudes compared to baseline and the highest and lowest doses are significantly different in their effect. There are no remarkable differences in the clinical exams, fundus images, or fluorescent angiograms with doses of 10mg/kg or less. The retinas of 37% of the pigs which received 7.5 to 20mg/kg IAA had thinner retinal vessels and pale optic discs. Histological sections corroborated our ffERG results. Morphological damage is confined to the photoreceptors and the number of nuclei in the outer nuclear layer (ONL) decreases with increasing dose.
IAA is an effective toxin and creates selective and dosage controlled structural and functional damage of photoreceptors in domestic swine. NaIO3, however, is not effective in sub-lethal doses. Because of the controlled nature of the IAA-induced damage in the pig, it can be used to initiate damage, which can in turn be used to investigate the treatment or replacement of damaged photoreceptors in a large animal model of photoreceptor degeneration.
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