Alterations in Circulating Immune Cells in Neovascular Age-Related Macular Degeneration.

Judith Lechner,Mei Chen,Heping Xu,Giuliana Silvestri,Ruth E Hogg,Levente Toth,Usha Chakravarthy

doi:10.1038/srep16754

Abstract

Neovascular age-related macular degeneration (nAMD) is the leading cause of irreversible blindness in developed countries. Recent advances have highlighted the essential role of inflammation in the development of the disease. In addition to local retinal chronic inflammatory response, systemic immune alterations have also been observed in AMD patients. In this study we investigated the association between the frequency of circulating leukocyte populations and the prevalence as well as clinical presentations of nAMD. Leukocyte subsets of 103 nAMD patients (most of them were receiving anti-VEGF therapy prior to enrolment) and 26 controls were analysed by flow cytometry by relative cell size, granularity and surface markers. Circulating CD11b+ cells and CD16hiHLA-DR− neutrophils were significantly increased (P = 0.015 and 0.009 respectively) in nAMD when compared to controls. The percentage of circulating CD4+ T-cells was reduced in nAMD patients without subretinal fibrosis (P = 0.026) compared to patients with subretinal fibrosis. There was no correlation between the percentage of circulating leukocytes and the responsiveness to anti-VEGF therapy in nAMD patients. Our results suggest that higher levels of circulating CD11b+ cells and neutrophils are associated with nAMD and that reduced levels of CD4+ T-cells are associated with the absence of subretinal fibrosis in nAMD.

Highlights

Age related macular degeneration (AMD) is the leading cause of blindness in the developed world in individuals above the age of 551,2
There was no correlation between the number of anti-VEGF injections received and the percentage of lymphocytes (R2 = 0.16; P = 0 .105, Fig. 1a), neutrophils (R2 = −0.09; P = 0 .376, Fig. 1b), neutrophil/lymphocyte ratio (NLR) (R2 = −0.15; P = 0.137, Fig. 1c), CD11b+ cells (R2 = −0.11; P = 0.370, Fig. 1d), CD16hiHLA-DR− neutrophils (R2 = −0.15; P = 0.136, Fig. 1e), CD16hiHLA-DR−/(CD4 + CD8) ratio (R2 = −0.17; P = 0.105, Fig. 1f) and CD16hiHLA-DR−/CD8 ratio (R2 = −0.07; P = 0.490, Fig. 1g)
In addition to increased levels of complement components and pro-inflammatory cytokines in the serum of AMD patients[17,18], changes in leukocytes, especially monocytes have been reported in AMD20–22

Summary

Introduction

Age related macular degeneration (AMD) is the leading cause of blindness in the developed world in individuals above the age of 551,2. When abnormal neovascular complexes are present under the retinal pigment epithelium this is referred to as type 1 choroidal neovascularisation (CNV). When these complexes invade the subretinal space these are referred to as type 2 membranes[4]. P value nAMD vs Control patients[14] and histological studies have detected macrophages in the vicinity of drusen[15] as well as in retinal lesions[16] in eyes from AMD patients, suggesting a local chronic inflammatory response in AMD. In addition to the local inflammatory response, systemic immune alterations have been observed in AMD patients. Increased serum levels of complement components[17] and pro-inflammatory cytokines such as IL-1α , IL-1β and IL-1718 have been reported in patients with AMD. Due to lack of knowledge in the detailed immune pathways involved in nAMD, more effective immune therapy has yet to be developed

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Results

Conclusion