Abstract
Purpose: :
Iodoacetic acid (IAA) induces photoreceptor (PR) degeneration in several species, and the anatomical and physiological consequences of IAA have been explored in the rabbit. However, rabbit eyes differ considerably from human eyes and are not the best model for studies related to human retinal degenerations. Porcine eyes are anatomically closer to human eyes and are commonly used for the development and testing of therapeutic strategies for treating human disease. Therefore, this study investigated whether IAA treatment also induces photoreceptor degeneration in porcine eyes, which would have potential uses in the development of therapies relevant to human disease.
Methods: :
Pigs were given a single injection of IAA i.v. (5.0 mg/kg, N=3; 7.5 mg/kg, N=4; 10.0 mg/kg, N=4; 12.0 mg/kg, N=3) and were euthanized 2-5 weeks later. Eyes were also studied from 9 control pigs. Eyes were fixed in 2% paraformaldehyde & 2% glutaraldehyde in PO4 buffer. A vertical strip of retina spanning from the superior to inferior retinal quadrants was processed for light microscopy. To quantify PR degeneration, rows of nuclei in the outer nuclear layer were counted 8 mm above the dorsal margin of the disc, 1.4 mm dorsal to the disc, 1.4 mm and 8 mm below the disc.
Results: :
All pigs treated with IAA at 10.0, and 12.0 mg/kg exhibited a PR layer that was significantly thinner in all tested locations, compared to control eyes. Pigs treated with 7.5 mg/kg were less severely affected, although all but two locations in two eyes had a significant reduction in rows of PR nuclei, compared to controls. The effect of 5 mg/kg was weak, with small but significant reductions in only one animal.
Conclusions: :
IAA at 7.5-12.0 mg/kg in the pig induces rapid, robust PR degeneration. This may be a useful model for development of interventions that can eventually be applied to humans with PR degeneration.
Keywords: drug toxicity/drug effects • retina • microscopy: light/fluorescence/immunohistochemistry