Characterization of a mouse model of RPE pathology

Abstract

Purpose : Systemic or intraocular sodium iodate (NaIO₃), an oxidizing agent, induces severe retina/RPE pathology in mice. Most published studies have analyzed acute effects of high doses of sodium iodate or long term studies after low doses, but without longitudinal structure and functional correlation. We characterized the dose responsive and time course effects of lower doses of NaIO₃ administered by two routes of administration on mouse ocular structure and function.

Methods : Sodium Iodate was administered via intraperitoneal (IP) or intravenous (IV) routes at 1, 3, 10 or 15 mg/kg in C57BL/6J mice (n = 5 or more animals per group). Retinal thickness was quantified from optical coherence tomography (OCT) with b-scans centered on the optic nerve (Envisu, Bioptigen). Qualitative assessment of retinal health was performed using the fluorescein channel autofluorescence (AF) and infrared (IR) reflectance mode of a scanning laser ophthalmoscope (SLO) with a 55 degree lens (Spectralis, Heidelberg Engineering). Visual acuity (VA) was assessed using an OptoMotry HD (CerebralMechanics).

Results : Mice challenged with 15 mg/kg, but not lower doses of sodium iodate, administered IP or IV developed ocular abnormalities by OCT/SLO at 1-week post injection. Retinal thinning and RPE pathology were more consistent with IV dosing (5/5 eyes) compared to IP (3/5). The structuralpathology in mice challenged with 15 mg/kg IV NaIO₃ was associated with a significant reduction in VA which progressively declined from baseline by ↓17.9 ± 2.1% at one week to ↓61.1 ± 5.7% at two weeks post-injection. In contrast, VA and retinal thickness did not significantly decline in IP challenged mice. Retinal thinning progressed from week 1 to week 2, although the rate of loss was less pronounced than the rate of reduction in vision (↓20.1% or -44 ± 2.4 µm p<0.0001 at week 1 ↓26 ± 1.5% -57 ± 3.3 µm at week 2).

Conclusions : Intravenous administration of 15 mg/kg of sodium iodate induces consistent retinal/RPE abnormalities in C57BL/6J mice. The majority of the structural loss is one week post-challenge, while visual functional decline accelerates between week 1 and 2. This in vivo model may have utility in the study of retina/RPE pathology.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.