| 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 rods and cones. This study investigated whether IAA also produced PR degeneration in the porcine retina, whether the damage was preferential for rods or cones, and whether IAA induced remodeling of the remaining neurons. Pigs (ages 6–8 weeks) were given a single i.v. injection of IAA and were euthanized 2–5 weeks later. Eyes were enucleated and retinal tissue was processed for conventional histology, immunohistochemistry, and transmission electron microscopy. At 5.0 mg/kg IAA produced mild, variable cell loss, but the remaining cells exhibited normal features. At doses above 5.0 mg/kg, a dose-dependent reduction was observed in the length of PR inner and outer segments, and in the number of total PR nuclei. IAA at 7.5 or 10.0 mg/kg reduced the number of rows of rod cell bodies in all tested locations, and caused a loss of cone outer segments, and a significant reduction in the frequency of cone pedicles, without inducing a significant loss of cone cell nuclei. Pigs treated with 12.0 mg/kg IAA were most severely affected: rods were virtually eliminated, cone nuclei were pyknotic, cone cytoplasm was swollen, and cone pedicles were significantly reduced. Dendritic retraction of rod bipolar cells and hypertrophy of Müller cell stalks was also observed, although the inner nuclear layer appeared intact. Therefore, IAA at 7.5–12.0 mg/kg in the pig induces rapid, robust PR degeneration. 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. |
