Peripheral blood CD163(+) monocytes and soluble CD163 in dry and neovascular age‐related macular degeneration

Abstract

Macrophages are the main infiltrating immune cells in choroidal neovascularization (CNV), a hallmark of the human wet, or neovascular age‐related macular degeneration (AMD). Due to their plasticity and ability to adapt to the local microenvironment in a tissue‐dependent manner, macrophages display polar functional phenotypes characterized by their cell surface markers and their cytokine profiles. We found accumulation of hemoglobin‐scavenging cluster of differentiation 163 (CD163)(+) macrophages in laser‐induced CNV lesions and higher expression of CD163(+) monocytes in the peripheral blood on day 7 post injury in mice. In comparison, CD80(+) macrophages did not differ with laser‐injury in young or aged mice and did not significantly change in the peripheral blood of CNV mice. We examined the percentages of CD163(+), CD206(+), and CD80(+) monocytes in the peripheral blood of patients with wet AMD, patients with dry AMD, and in age‐matched individuals without AMD as controls. Percentages of peripheral blood CD163(+) monocytes in both dry AMD (P < .001) and wet AMD (P < .05) were higher than in age‐matched non‐AMD controls, while there was no difference between the groups in the percentages of peripheral CD206(+) and CD80(+) monocytes. Further, serum level of soluble CD163 (sCD163) was elevated only in patients with wet AMD (P < .05). An examination of 40 cytokine levels across the study groups revealed that anti‐VEGF treated patients with wet AMD, who showed no exudative signs on the day of blood drawing had a cytokine profile that was similar to that of non‐AMD individuals. These results indicate that CD163 could be further evaluated for its potential as a useful marker of disease activity in patients with neovascular AMD. Future studies will address the origin and potential mechanistic role of CD163(+) macrophages in wet AMD pathologies of angiogenesis and leakage of blood components.

Long-Chain Polyunsaturated Fatty Acids and Their Metabolites Regulate Inflammation in Age-Related Macular Degeneration

“…[162][163][164] M2-like macrophages produced MMPs, which enhanced the penetration of CNV through Bruch's membrane, while M1 macrophages ameliorated CNV. [165][166][167][168][169] Previous studies also showed that CNV could be inhibited by downregulating M1 macrophage/microglia polarization. 170 Allingham et al suggested that the early recruitment of inflammatory M1 macrophages promoted the induction and initial development of CNV, followed by the sustained recruitment of reparative M2 macrophages that mediated the sustained CNV formation and growth.…”

Myeloid cells in retinal and brain degeneration

“…Macrophages are the primary infiltrating immune cells in choroidal neovascularization (CNV), a hallmark of exudative AMD [126]. Higher levels of MCP‐1 have been identified in the serum of patients with exudative AMD compared with unaffected age‐ and gender‐matched controls [127].…”

“…The monocyte marker CD163, along with other cytokines implicated in inflammation, may be an indicator of disease status in AMD. The levels of multiple cytokines including CD163 in the peripheral blood of human patients differed between exudative AMD, nonexudative AMD, and age‐matched controls, depending on the presence of active leakage in exudative cases [126]. Higher peripheral blood levels of C‐reactive protein and IL‐6, for example, have been associated with AMD progression [129,130].…”

Tumor‐associated macrophages as treatment targets in glioma

“…The therapeutic effect of CHA is due to repolarization of M2 macrophages to M1. Plasticity and mobility are hallmarks of TAMs [84], and TAMs can be remodeled by a CHA‐educated TME. CHA therapy for patients with glioma can skew the macrophages in the TME away from the M2 phenotype and toward the M1 phenotype by stimulating STAT1 and repressing the STAT6 signal pathway.…”