Electrophysiologic and Morphologic Strain Differences in a Low-Dose NaIO(3)-Induced Retinal Pigment Epithelium Damage Model

PURPOSE: We aimed to explore differences in the NaIO(3)-elicited responses of retinal pigment epithelium (RPE) and other retinal cells associated with mouse strains and dosing regimens. METHODS: One dose of NaIO(3) at 10 or 15 mg/kg was given intravenously to adult male C57BL/6J and 129/SV-E mice. Control animals were injected with PBS. Morphologic and functional changes were characterized by spectral domain optical coherence tomography, electroretinography, histologic, and immunofluorescence techniques. RESULTS: Injection with 10 mg/kg of NaIO(3) did not cause consistent RPE or retinal changes in either strain. Administration of 15 mg/kg of NaIO(3) initially induced a large transient increase in scotopic electroretinography a-, b-, and c-wave amplitudes within 12 hours of injection, followed by progressive structural and functional degradation at 3 days after injection in C57BL/6J mice and at 1 week after injection in 129/SV-E mice. RPE cell loss occurred in a large posterior-central lesion with a ring-like transition zone of abnormally shaped cells starting 12 hours after NaIO(3) treatment. CONCLUSIONS: NaIO(3) effects depended on the timing, dosage, and mouse strain. The RPE in the periphery was spared from damage compared with the central RPE. The large transient increase in the electroretinography was remarkable. TRANSLATIONAL RELEVANCE: This study is a phase T1 translational research study focusing on the development and validation of a mouse model of RPE damage. It provides a detailed foundation for future research, informing choices of mouse strain, dosage, and time points to establish NaIO(3)-induced RPE damage.