Plasma concentrations of inflammatory chemokines in intermediate and advanced atrophic age-related macular degeneration stratified by sex

Abstract

Purpose : Alterations in the innate immune system leading to local inflammation have been implicated in the pathogenesis of age-related macular degeneration (AMD). However, the role of specific chemokines has been less explored. Chemokines such as CCL2 or macrophage chemoattractant protein-1 (MCP-1) have been shown to be higher in neovascular AMD eyes and implicated in inducing RPE apoptosis. CCL3 and CCL4, also referred to as macrophage inflammatory protein-1 alpha and beta (MIP-1a and MIP-1b), recruit macrophages and microglia and can induce a pro-inflammatory state. The purpose of this study was to examine the association between systemic levels of inflammatory chemokines and AMD in patients with intermediate AMD (iAMD) and advanced AMD with geographic atrophy (GA) and to determine if these chemokines were moderated by sex.

Methods : Blood samples were collected from patients enrolled into the University of Colorado AMD Registry from August 2014 to June 2021. iAMD and GA cases were defined by multimodal imaging. Concentrations of chemokines CCL2/MCP-1, CCL3/MIP-1a, and CCL4/MIP-1b were measured using multiplex immunoassays. A non-parametric rank-based linear regression model was fit to plasma chemokines with sex by AMD category interaction.

Results : 208 iAMD patients, 96 patients with GA, and 128 controls were included in this study. Median concentrations of CCL3/MIP-1a were significantly decreased in iAMD cases compared to controls and in GA cases compared to iAMD cases (Table 1). After stratifying by sex, levels of CCL4/MIP-1b and CCL2/MCP-1 were not significantly elevated in GA compared with controls. However, within the GA group, female cases showed decreased levels of CCL4/MIP-1b compared to males.

Conclusions : Systemic levels of CCL4/MIP-1b and CCL2/MCP-1 were not significantly increased in iAMD and GA cases. These results are not aligned with the findings of other study that have demonstrated increased levels of these chemokines in neovascular AMD, even after stratifying by sex. Our findings of significantly decreased levels of CCL3/MIP-1a in AMD cases compared to controls may be related to its paradoxical effects in acute versus chronic retinal degeneration as demonstrated in mouse models, but future research elucidating its role is needed.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.