Preferential Loss of Cone Photoreceptors and Light-Adapted Cone Function in an Iodoacetic Acid Model of Photoreceptor Damage in the Rabbit Retina

Abstract

Purpose: : This work is related to the efforts of the Boston Retinal Implant Project to develop a sub-retinal prosthesis to restore vision to the blind. The specific purpose of this study was to analyze regional photoreceptor damage in the neurosensory retina (NSR) of rabbits following systemic injection of the photoreceptor toxin, iodoacetic acid (IAA), and relate these changes to rod and cone function using the full field electroretinogram (ERG).

Methods: : Four adult Dutch-belted rabbits were given an intravenous injection of IAA (20 mg/kg body weight). Dark-adapted and light-adapted baseline ERGs were recorded before injection and at 2 weeks, 1, 3 and 6 months following injection. Retinal morphology was assessed by light microscopy (LM) and immunohistology (IH) at 6 months post injection.

Results: : Histological assessment in IAA treated animals showed damage confined to photoreceptors. Photoreceptor loss was most severe in the visual streak, with an almost complete loss of photoreceptors. Photoreceptor loss diminished dorsally and ventrally as a function of distance from the visual steak. Photoreceptor damage was well correlated with differential changes in the ERG. The b-wave amplitude of the dark-adapted ERG remained relatively normal, showing an average baseline amplitude of 174.4 ± 18 µV compared to 185.6 ± 18.2 µV (p>0.01) 6 months after injection. In contrast, the b-wave amplitude of the light-adapted ERG was greatly diminish from a baseline amplitude of 124.1 ± 14.9 µV to 71.6 ± 9.4 µV at 6 months (p<0.01).

Conclusions: : At this dose, the toxic effects of IAA were found primarily in the photoreceptors in the visual streak. This damage led to a selective loss of light-adapted cone-mediated signaling, whereas residual rod function in the periphery of the retina prevented a significant loss in signaling via rod photoreceptors in the dark-adapted ERG.

Keywords: drug toxicity/drug effects • electrophysiology: non-clinical • microscopy: light/fluorescence/immunohistochemistry