Increased Sodium Iodate-Induced Retinal Degeneration in the Presence of Systemic Inflammation Caused by Collagen-Induced Arthritis

Abstract

Purpose : Age-related macular degeneration (AMD) is the leading cause of blindness in the US. Diagnosed as either the wet (exudative or neovascular) or dry (non-exudative or atrophic) form, this disease is characterized by increased inflammation, oxidative stress and cytokine response, and deregulation of the complement system. Rheumatoid arthritis (RA) shares many risk factors with AMD and triggers a similar inflammatory response. Recent data from our laboratory has identified an increased risk of dry AMD among RA patients using retrospective patient data analysis. Additionally, we found that laser-induced choroidal neovascularization, a model for wet AMD, is reduced in the presence of collagen-induced arthritis (CIA). In this current study, we further investigate the role of systemic inflammation on AMD using a mouse model for dry AMD.

Methods : CIA was induced in C57BL/6J mice using an emulsion of complete Freund's adjuvant and type II collagen, followed by induction of retinal degeneration by sodium iodate (NaIO₃) at the peak of CIA. Retinal structure/function was assessed by Optical Coherence Tomography (OCT) and electroretinography (ERG), and RPE morphology was examined by immunohistochemistry (ZO-1). 3-6 mice were analyzed per group and timepoint.

Results : NaIO₃ treatment resulted in a significant decrease in whole retinal thickness when compared to both control and CIA treated animals (p≤0.001). NaIO₃ treatment in the presence of CIA resulted in further loss of retinal thickness (p≤ 0.05). Following staining with ZO-1, we observed that NaIO₃ treatment resulted in loss of the normal RPE hexagonal shape, which was further aggravated by the presence of CIA. C-wave analysis was found to be significantly reduced for NaIO₃ mice, independent of the presence or absence of CIA (p ≤0.001).

Conclusions : Our OCT and immunohistochemistry data demonstrates that increased systemic inflammation caused by RA leads to increased retinal damage in the NaIO₃ model of retinal degeneration. These results further support our retrospective patient data analysis, which finds that RA patients are at increased risk of dry AMD. These preliminary findings highlight the need for further investigation of the role of secondary inflammation on dry AMD.

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