Age-related macular degeneration is associated with increased plasma levels of soluble TNF receptor II

Abstract

Purpose: Age-related macular degeneration (AMD) is a common disease of the aged population. We have recently identified homeostatic alterations in the circulating T cells in patients with AMD. In cultures of retinal pigment epithelial (RPE) cells, we have demonstrated that T cell-derived cytokines induced the upregulation of complement, chemokines and other proteins implicated in AMD pathogenesis. The purpose of this study was to test whether the plasma levels of RPE and T cell-associated cytokines were increased in patients with AMD.

Methods: To test this, we conducted a case-control study in a clinical setting. AMD status was assessed using standardized multi-modal imaging techniques. Plasma was isolated from freshly drawn peripheral blood samples and analyzed for interleukin (IL)15, IL18, interferon (IFN)γ, soluble tumor necrosis factor (TNF) receptor II (sTNFRII, a pseudo-marker of TNFα) and complement factor H Y402H genotype.

Results: We included 136 individuals with early or late (exudative and atrophic) forms of AMD and 57 aged controls. While no associations were found between plasma levels of IL15, IL18 or IFNγ, significantly increased levels of sTNFRII were observed in patients with early or exudative AMD. Further, based on the plasma level of sTNFRII, individuals in the middle tertile had a higher multivariate-adjusted odds ratio for prevalence of any form of AMD than individuals in the highest tertile.

Conclusions: Together, these data support the observations of systemic inflammatory alterations in patients with AMD. Further, we suggest that a low level of inflammation confers greater risk of AMD than a high level of inflammation, which may imply that inflammation also has beneficial effects in the context of AMD.

Keywords: 412 age-related macular degeneration • 557 inflammation • 490 cytokines/chemokines