Sodium Iodate: Rapid and Clinically Relevant Model of AMD

Abstract

Background: Age-related macular degeneration (AMD) is the most common cause of vision loss in people above the age of 50, affecting approximately 10% of the population worldwide and the incidence is rising. Hyperreflective foci (HRF) are a major predictor of AMD progression. The purpose of this study was to use the sodium iodate mouse model to study HRF formation in retinal degeneration.

Methods: Sodium iodate (NaIO₃) treated rodents were studied to characterize HRF. 3-month-old male wild-type (WT) C57Bl/6J mice were injected with phosphate-buffered saline (PBS) or varying doses of NaIO₃ (15-60 mg/kg). Optical Coherence Tomography (OCT) images were collected at baseline and several days post-NaIO₃ injection. Retinal thicknesses were measured using Bioptigen software. Seven days post-injection, eyes were prepared for either transmission electron microscopy (TEM), Hematoxylin & Eosin (H&E), or immunofluorescence.

Results: OCT imaging of the mice given higher doses of NaIO₃ revealed HRF formation in the neural retina (n = 4). The amount of HRF correlated with the degree of retinal tissue loss. H&E and TEM imaging of the retinas seven days post-NaIO₃ injection revealed several pigmented bodies in multiple layers of the retina (n = 3-5). Immunofluorescence revealed that some pigmented bodies were positive for macrophage markers and an epithelial-to-mesenchymal transition marker, while all were retinal pigment epithelium (RPE) 65-negative (n = 4).

Conclusions: The data suggest that NaIO₃ induces the formation of HRF in the outer retina and their abundance correlates with retinal tissue loss. The experiments in this study highlight NaIO₃ as a clinically relevant model of intermediate AMD that can be used to study HRF formation and to discover new treatment targets.

Keywords: epithelial-to-mesenchymal transition; hyperreflective foci; macular degeneration; retinal pigment epithelia.