Retinal phenotypic differences between two dry age-related macular degeneration rat models

Abstract

Purpose : Development of nongenetic animal models that mimic the human disease phenotypes is essential to test the efficacy of novel ocular therapies. We compared differences in the retinal phenotypes between two rat models, sodium iodate (NaIO3) and intense bright white light exposure, that have been used extensively to evaluate novel therapies for dry age-related macular degeneration (dAMD).

Methods : Thirty 8–10-weeks-old male Sprague Dawley (SD) rats were enrolled. Saline (N=5) or NaIO3 (40 mg/kg, N=15) was administered intravenously. Ten rats were exposed either to standard room light (N=3) or 6000 lux white light intensity for 1 hour (N=3) or 3 hours (N=4) after 14-16 hours of dark adaptation. Following the treatment, animals were maintained under a standard 12-hour light/ 12-hour dark cycle. Clinical ophthalmic examinations (OE), autofluorescence (AF) imaging, and optical coherence tomography (OCT) were performed at baseline and post-treatment at 24 hours, 72 hours and at Day 7. Light exposed animals were evaluated for an additional 2 weeks. Inferior, center and superior retinal regions were selected for total retinal and outer nuclear layer (ONL) thickness analysis using OCT.

Results : Minimal changes in the retina were observed in the NaIO3 model, however, light exposed animals developed diffuse hyperreflective retinal lesions and decreased ONL thickness at 24 hours. An increase in the retinal AF was detected over time in both models. On Day 7, NaIO3 had disruption of the inner and outer segment (IS/OS) junction of ONL, retinal pigment epithelial (RPE) shedding and migration into the ONL and disrupted outer plexiform layer in the inferior region of the retina. In contrast, light exposed animals had homogeneous RPE layer attenuation and significantly (p < 0.05) degenerated photoreceptors in the superior retina compared to controls. Total retinal and ONL thickness were significantly (p < 0.05) decreased at 1 and 2 weeks time points compared to Day 1 in light exposed animals.

Conclusions : Both models partially mimic human dAMD condition. Significant RPE degeneration with minimal ONL degradation were observed in NaIO3 model, while complete ONL and significant RPE degeneration at later stage were featured in the light exposed animals. These models provide a reliable and acute method to study the pathological mechanism of dAMD and to evaluate novel therapeutic strategies.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.