Retinal Histology 14 Days to 6 Months After Systemic Iodoacetic Acid (IAA) Administration

Abstract

Abstract: : Purpose: To characterize the pattern of retinal degeneration in the rabbit retina at different survival intervals after a single intravenous injection of IAA, a known toxin for photoreceptors. Methods: A single dose of sterile iodoacetic acid (20 mg/kg i.v.) was administered to Dutch–belted rabbits via the ear vein. After a survival interval of 14 days, 1 month, 3 months or 6 months the rabbits were euthanized, the eyes fixed in 4% paraformaldehyde and the retinas were prepared for conventional histology using plastic sections and for immunohistochemistry using cryostat sections. Results: Damage to the outer nuclear layer (ONL) was most common in the region of the visual streak and in the ventral retina. The far peripheral margins of the retina were spared from the effects of the IAA, even in cases in which damage to the ONL was extensive throughout the rest of the retina. In damaged regions of the retina at 14 days – 3 months survival the ONL was completely missing in some cases, in others it was significantly reduced in thickness, and sometimes it appeared to be normal. At 6 months the ONL in the visual streak was somewhat reduced in thickness but appeared healthy. Wherever photoreceptors survived they were immunopositive for opsin. Horizontal cells appeared to remain intact, as judged by the pattern of calbindin–D28 labeling. In locations in which the ONL was completely destroyed, the horizontal cells abutted the RPE. Conclusions: The susceptibility of photoreceptors to iodoacetic acid varied across the retina, and from animal to animal at the same survival interval. Less damage was observed after a 6 month–survival than at shorter intervals, raising the possibility of long–term recovery. In general, the histology in a given animal was reflected by physiological measures (ERG, VEP) in concomitant experiments.

Keywords: pathology: experimental • retina: distal (photoreceptors, horizontal cells, bipolar cells) • microscopy: light/fluorescence/immunohistochemistry