Macrophage polarization in the maculae of age‐related macular degeneration: A pilot study

Abstract

Macrophages can be polarized to exhibit either pro-inflammatory M1 or pro-angiogenic M2 phenotypes, but have high phenotypic plasticity. This pilot study investigated macrophage polarization in the macular retina and choroid of age-related macular degeneration (AMD) and non-AMD subjects, as well as in AMD choroidal neovascular membranes (CNVM). All specimens were evaluated for routine histopathology. Quantitative real-time polymerase chain reaction for representative M1 (CXCL11) and M2 (CCL22) transcripts were performed on macular choroidal trephines (MCT) of 19 AMD and nine non-AMD eye bank eyes, on the microdissected macular retinal cells from the archived slides of five geographic atrophic AMD, five exudative/neovascular AMD, and eight normal autopsied eyes, and on microdissected inflammatory cells from two surgically removed CNVM that did not respond to anti-vascular endothelial growth factor (VEGF) therapy. High M2-chemokine transcript and a low ratio of M1 to M2 chemokine transcript were found in aging non-AMD MCT. Advanced AMD maculae had a higher M1 to M2 chemokine transcript ratio compared to normal autopsied eyes. Macrophages in the two CNVM of patients unresponsive to anti-VEGF therapy were polarized toward either M1 or M2 phenotypes. The number of M2 macrophages was increased compared to M1 macrophages in normal aging eyes. A pathological shift of macrophage polarization may play a potential role in AMD pathogenesis.

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“…40 But inhibiting the effect of macrophage (M1) was not sufficient for prevention GA. 41 Moreover, T-cell subsets could modulate macrophage polarization (such as Th1, which is related to M1 immune response). 42 So, in this study we researched the effects of RPE cells in modulating T-cell immunity in the immune pathological progression of AMD through in vitro cell models.…”

Exosomes from Retinal Astrocytes Contain Antiangiogenic Components That Inhibit Laser-induced Choroidal Neovascularization

“…Infiltrating macrophages play an important role in exudative AMD (30,31) and in experimental CNV (32,33). They are a major source of inflammatory cytokines, complement, and VEGF, all of which are important in the pathogenesis of inflammation and new vessel formation.…”

Doyne lecture 2016: intraocular health and the many faces of inflammation

“…[75][76][77] Furthermore, both macrophages and multinucleated giant cells, mainly associated with vascular channels and breaks in Bruch's membrane are evident. [78][79][80][81][82][83] Macrophage subtype changes have been noted in the eyes of patients with AMD, including a change in the M1/M2 ratio in AMD eyes, compared with that in control eyes of the same age. 83 With all the data demonstrating immune activation, we need to reconcile these findings with the knowledge that the development of AMD is slow.…”

“…[78][79][80][81][82][83] Macrophage subtype changes have been noted in the eyes of patients with AMD, including a change in the M1/M2 ratio in AMD eyes, compared with that in control eyes of the same age. 83 With all the data demonstrating immune activation, we need to reconcile these findings with the knowledge that the development of AMD is slow. First, given that AMD is insidious, altered immune responses within the tissue likely occur as a result of persistent lifetime oxidative stress and changes to cell health in the retina.…”