Systemic inflammation in a collagen-induced arthritis mouse model of rheumatoid arthritis leads to attenuated laser-induced choroidal neovascularization

Abstract

Purpose : Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in the U.S. Current research suggests that AMD is characterized by inflammation and deregulation of the complement cascade, as well as oxidative stress and cytokine response. These characteristics are also present in rheumatoid arthritis (RA), a painful disease resulting in inflammation of the joints. While AMD shares similarities with RA, the role of a secondary inflammatory disease on AMD pathogenesis is largely unknown. Using mouse models, this study investigates the role of RA on laser induced choroidal neovascularization (CNV), a model for wet AMD.

Methods : Collagen-induced arthritis (CIA) was induced in C57BL/6J mice by immunization with collagen type II in adjuvant followed by induction of CNV at the peak of disease. CNV lesion size was quantified using optical coherence photography (OCT). Functional differences between CIA and control mice in the absence and presence of CNV was analyzed using optokinetic response (OKR) to measure spatial acuity and contrast sensitivity, as well as full-field electroretinography (ERG) to examine retina and RPE function.

Results : OKR analysis of CIA mice compared to controls indicated a significant decrease in both spatial acuity (control: 0.37 ± 0.009; CIA: 0.32 ± 0.011: p ≤ 0.01) as well as contrast sensitivity (control: 5.85 ± 0.63; CIA: 2.99 ± 0.38; p ≤ 0.001), whereas no differences were observed for a-, b- and c-wave analyses. Surprisingly, systemic inflammation caused by CIA resulted in significantly reduced CNV lesion size (control: 8530 ± 496.3µm²; CIA: 5961 ± 481.9 µm²; p ≤ 0.001). Functional differences after CNV are forthcoming.

Conclusions : Our data demonstrated that increased systemic inflammation caused by CIA reduced both spatial acuity and contrast sensitivity, features that assess ocular and CNS function, whereas the purely retinal or RPE readouts (ERG) were unaffected. CIA was observed to attenuate CNV lesion size, suggesting that despite sharing similarities in etiology, CIA and CNV were not additive. It will be of great interest to determine whether RA reduces the risk of developing wet AMD in patients. Finally, these results highlight the need to further investigate the impact of a secondary inflammatory disease on wet and dry AMD.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.