Systemic Inflammation by Collagen-Induced Arthritis Affects the Progression of Age-Related Macular Degeneration Differently in Two Mouse Models of the Disease

Purpose: Age-related macular degeneration (AMD) shares similar risk factors and inflammatory responses with rheumatoid arthritis (RA). Previously, we identified increased risk for dry AMD among patients with RA compared to control subjects, using retrospective data analysis. In this current study, we investigate the role of systemic inflammation triggered in a murine model of arthritis on choroidal neovascularization and retinal pigment epithelium (RPE) degeneration mouse models. Methods: Collagen-induced arthritis (CIA) was induced in C57BL/6J mice prior to laser-induced choroidal neovascularization (CNV; wet AMD model) or sodium iodate–induced retinal degeneration (NaIO3; dry AMD model). CNV lesion size and retinal thickness were quantified by optical coherence photography (OCT), visual function was analyzed using optokinetic response and electroretinography, RPE morphology was examined by immunohistochemistry, and inflammatory gene expression was analyzed by quantitative PCR. Results: CIA mice demonstrated decreased spatial acuity and contrast sensitivity, whereas no difference was observed in the RPE-generated c-wave. CNV lesion size was decreased in CIA mice. NaIO3 decreased c-wave amplitude, as well as retinal thickness, which was augmented by CIA. NaIO3 treatment resulted in loss of normal RPE hexagonal shape, which was further aggravated by CIA. Increased Cxcl9 expression was observed in the presence of CIA and CIA combined with AMD. Disease severity differences were observed between sexes. Conclusions: Our data suggest systemic inflammation by CIA results in increased pathology in a dry AMD model, whereas it reduces lesions in a wet AMD model. These findings highlight the need for additional investigation into the role of secondary inflammation and sex-based differences on AMD.