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

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.