Electrophysiological and morphological changes in a low dose sodium iodate induced RPE damage model

Abstract

Purpose : Sodium iodate (NaIO₃) is selectively toxic to retinal pigment epithelium (RPE), inducing RPE cell death and subsequent photoreceptor degeneration. We explored differences in NaIO₃-elicited responses of RPE and other retinal cells associated with mouse strains and dosing regimens.

Methods : A single dose of NaIO₃ at 15 mg/kg was injected intravenously into adult male C57BL/6J and 129/SV-E mice while control animals were injected with the vehicle (PBS). Morphological and functional changes were characterized by fundus imaging, spectral domain optical coherence tomography (SD-OCT), ERG, histological, and immunofluorescence techniques.

Results : The 15 mg/kg NaIO₃ dose initially induced a transient increase in scotopic ERG a- ,b-wave and c-wave amplitudes in 12 hours post-injection, followed by progressive structural and functional degradation at 3 days in C57BL/6J and at 1 week in 129/SV-E mice, including depression of ERG response, loss of RPE cells, retinal structure disruption, and thinning of retinal thickness. Strain-difference existed in these two strains: 129SV-E mice showed slower photoreceptor degeneration (7 days post-injection) compared with C57BL/6J mice (3 days post-injection), which indicated that C57BL/6J mice are more sensitive to toxicity of NaIO₃. Immunofluorescence imaging revealed Müller cell activation following NaIO₃ administration. RPE cell death occurred in a large posterior-central lesion, with a ring-like transition zone of highly irregular, abnormally shaped cells that appeared as early as 12 hours after NaIO₃ treatment in both strains. RPE cells in the far periphery survived with generally normal morphology.

Conclusions : The morphological and functional effects of NaIO₃ on RPE and retina were dependent on timing, dosage, and strain of mouse. Transient rise and fall of ERG response were thoroughly characterized in both strains. Far peripheral RPE cells were much more resistant to damage than central RPE. It may be that peripheral vs central RPE cells have fundamentally different properties, or location-specific factors mediate these differences in resiliency.

This is a 2021 ARVO Annual Meeting abstract.