Evidence for systemic immune activation in patients with ARMD

Abstract

Abstract: : Purpose: To search for evidence of systemic immune activation in patients with ARMD Methods: Heparinized blood from five patients (ages: 76 – 89; 4 men and 1 women) with various forms of ARMD, five elderly controls and a set of normal blood donors were evaluated by flow cytometry for variety of immunologic activation markers. Results: Two subsets of cells showed abnormal levels of immunologic activation in ARMD blood as compared to controls. The macrophage differentiation marker CD16 was elevated on the surface of a subset of CD14 expressing monocytes in ARMD blood as compared to controls (p<0.03). In conjunction with macrophage activation, T cell activation as manifested by elevation of the CD38 marker on the CD8 T cell subset was also elevated in ARMD as compared to controls.(p<0.04). The two patients with "dry" forms of ARMD showed the greatest levels of abnormality as compared to "wet" ARMD and controls. Conclusions:Data reported in this pilot study are consistent with a model of ARMD that involves a component of systemic immunologic activation. The systemic activation of both macrophages and T cells in ARMD might provide novel targets for the development of drugs to impact the immunologic aspects of ARMD pathogenesis. Blood derived activated macrophages serve as surrogates for the ARMD retinal macrophages and novel therapies directed against them could be monitored for efficacy through study of blood specimens in conjunction with retinal examination. Further studies will be required to confirm these observations, and if confirmed, drugs capable of modulating and/or killing the pathogenic macrophages might be considered as potential novel therapeutic agents in ARMD

Keywords: age–related macular degeneration • inflammation • immunomodulation/immunoregulation