Multimodal fundus imaging of sodium iodate-treated mice informs RPE susceptibility and origins of increased fundus autofluorescence

Abstract

PURPOSE. By multimodal imaging, and the use of mouse and in vitro models, we have addressed changes in fundus autofluorescence (488 and 790 nm) and observed interactions between the photooxidative stress imposed by RPE bisretinoid lipofuscin and the oxidative impact of systemic sodium iodate (NaIO3). METHODS. Abca4-/-, wild-type, and Rpe65rd12 mice were given systemic injections of NaIO3 (30 mg/kg). Analysis included noninvasive imaging of fundus autofluorescence (shortwavelength [SW-AF]; near-infrared excitation [NIR-AF]), quantitative fundus AF (qAF; 488 nm); light microscopy, RPE flat-mounts and measurements of outer nuclear layer (ONL) thickness. NaIO3 also was studied by using in vitro assays. RESULTS. In SW-AF and NIR-AF images, fundus mottling was visible 3 and 7 days after NaIO3 injection with changes being more pronounced in Abca4-/- mice that are characterized by an abundance of RPE bisretinoid lipofuscin. In Abca4-/- mice, qAF was elevated 3 and 7 days after NaIO3 administration. In light micrographs and RPE flat-mounts stained to reveal tightjunctions (ZO-1) and nuclei, the RPE monolayer was disorganized, and clumping and loss of RPE was visible. ONL thinning was most pronounced in Abca4-/- mice. Treatment of ARPE-19 cells with NaIO3 together with the photooxidation of the bisretinoid A2E by exposure to 430-nm light produced an additive effect whereby loss of cell viability was greater than with either perturbation alone. CONCLUSIONS. Elevations in SW-AF intensity can occur due to photoreceptor cell dysfunction as induced secondarily by NaIO3. Photooxidative stress associated with RPE cell bisretinoid lipofuscin may confer increased susceptibility to the oxidant NaIO3.