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Patrick A. Scott, Henry J. Kaplan, Julie H. Sandell; Iodoacetic Acid Affects Rods and Cones in the Porcine Eye. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4335.
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© ARVO (1962-2015); The Authors (2016-present)
Iodoacetic acid (IAA) induces photoreceptor (PR) degeneration in small animal models, however, small eye size and anatomic differences detract from the usefulness of these models for studying retinal rescue strategies intended for humans. Porcine eyes are closer in size to human eyes and have a rich supply of rod and cones. This study investigated whether IAA-induced degeneration in the porcine retina is preferential for rods vs. cones, and the effect of the toxin on the fine structure of the PRs.
Pigs were given one injection of IAA i.v. (5.0 mg/kg, N=7; 7.5 mg/kg, N=7; 10.0 mg/kg, N=7; 12.0 mg/kg, N=3) and were euthanized 2-5 weeks later. Eyes were also studied from 7 control pigs. Eyes were processed for immunohistochemistry or transmission electron microscopy (TEM). Rods were labeled with anti-Rho 4D2 and cones with peanut agglutinin (PNA). Rows of PR cell bodies in the outer nuclear layer were counted at 8 mm and 2 mm above the dorsal disc margin, and 2 mm and 8 mm below the disc. TEM was used to assess rod and cone fine structure in each location.
IAA at 5.0 mg/kg had no apparent effect on PRs. IAA at 7.5 and 10.0 mg/kg reduced the number of rows of rod cell bodies in all tested locations, with no significant reduction in cone cell bodies. TEM confirmed massive rod dropout, and also revealed loss of cone outer segments and a significant reduction in cone pedicles in at least two locations. Pigs treated with 12.0 mg/kg IAA were most severely affected: rods were virtually gone, cone nuclei were pyknotic, cone cytoplasm was swollen, and PR terminals were absent in all tested locations in one animal.
IAA at 7.5-12.0 mg/kg in the pig induces rapid, robust PR degeneration. Rods are more susceptible, but both cell types are affected. This model may be useful for developing and testing retinal rescue strategies for human diseases such as retinitis pigmentosa, in which rods are more susceptible than cones, or are affected earlier in the disease process.
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