Circulating Cytokine Profile in Age-Related Macular Degeneration

Abstract

Purpose: : Inflammatory biomarkers are increasingly valuable in identification of risk and pathogenic pathways with the aim of targeted treatment for many diseases. Age-related macular degeneration (AMD) has a complex multi-factorial aetiology with known underlying influence from the inflammatory cascade. This study investigated multiple serum and plasma cytokine levels in affected and normal subjects to evaluate the influence of systemic inflammatory markers in the pathogenesis of AMD.

Methods: : We examined 448 patients (248 in London and 200 in Southampton) with bio-microscopy, and retinal imaging in 2 independent cohorts. Health questionnaires were completed and collection of serum (London) and plasma (Southampton) samples with bilateral drusen, or exudative AMD with comparison to normal controls. These were analysed for 13 different cytokines using multiplex bead array and ELISA.

Results: : A significant difference in cytokine IL-6 levels was found in both the plasma and the serum cohorts with increased levels found in the CNV group (p<0.001). MCP-1 was found to be significantly (p< 0.04) reduced in the plasma CNV cohort with a similar trend seen in the serum group, however this did not reach significance. Neither age, sex nor smoking influenced the cytokine levels.

Conclusions: : Increased levels of IL-6 in the circulation is associated with increased risk for the development and progression of AMD independent of age or smoking status. MCP-1 is associated with the drive for macrophage attraction to sites of inflammation, reduced levels systemically may reflect a more localised influence of this cytokine, or an inability to mount a response due to defective MCP-1 recruitment leading to the development of uncontrolled inflammation and therefore CNV development.

Keywords: age-related macular degeneration • cytokines/chemokines