Systemic Inflammation by Collagen-Induced Arthritis Affects the Progression of Age-Related Macular Degeneration
Gloriane Schnabolk1, Elisabeth Obert1, Nirmal K Banda2
1Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina, United States.
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.
Insights
Systemic inflammation from rheumatoid arthritis worsened dry age-related macular degeneration (AMD) but reduced wet AMD lesions in mice. Sex differences in disease severity were also noted, requiring further study.
Area of Science:
- Ophthalmology
- Rheumatology
- Immunology
Background:
- Age-related macular degeneration (AMD) and rheumatoid arthritis (RA) share risk factors and inflammatory pathways.
- Previous studies indicated an increased risk of dry AMD in RA patients.
- This study explores the impact of systemic inflammation from arthritis on AMD models.
Purpose of the Study:
- To investigate how systemic inflammation, modeled by collagen-induced arthritis (CIA), affects choroidal neovascularization (wet AMD) and retinal pigment epithelium (RPE) degeneration (dry AMD) in mice.
- To analyze the consequences of CIA on visual function, RPE morphology, and inflammatory gene expression in AMD models.
Main Methods:
- Mice with CIA were subjected to laser-induced choroidal neovascularization (CNV) or sodium iodate-induced retinal degeneration (NaIO3).
- Measurements included CNV lesion size, retinal thickness (OCT), visual function (optokinetic response, electroretinography), RPE morphology (immunohistochemistry), and gene expression (qPCR).
Main Results:
- CIA mice showed reduced visual acuity and contrast sensitivity but no change in RPE c-wave. CNV lesion size was smaller in CIA mice.
- NaIO3-induced AMD showed decreased c-wave and retinal thickness, aggravated by CIA. RPE degeneration was worsened by CIA.
- Cxcl9 expression increased with CIA and combined CIA/AMD. Sex-based differences in disease severity were observed.
Conclusions:
- Systemic inflammation from CIA exacerbates dry AMD pathology while reducing wet AMD lesions.
- These findings underscore the complex role of secondary inflammation and sex differences in AMD pathogenesis.
- Further research is needed to elucidate these interactions for potential therapeutic strategies.
