title: 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.
authors: Immunopathology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, USA.
authors: Xiaoguang
authors: X
authors: Cao
authors: Defen
authors: D
authors: Shen
authors: Mrinali M
authors: MM
authors: Patel
authors: Jingsheng
authors: J
authors: Tuo
authors: T Mark
authors: TM
authors: Johnson
authors: Timothy W
authors: TW
authors: Olsen
authors: Chi-Chao
authors: CC
authors: Chan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016764:Cell Polarity; D054422:Chemokine CCL22 / Q000235:genetics; D054371:Chemokine CXCL11 / Q000235:genetics; D002829:Choroid / Q000473:pathology / Q000601:surgery; D020256:Choroidal Neovascularization / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D006801:Humans; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000166:cytology* / Q000276:immunology; D008266:Macula Lutea / Q000473:pathology*; D008268:Macular Degeneration / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D010641:Phenotype; D010865:Pilot Projects; D012333:RNA, Messenger / Q000235:genetics; D012160:Retina / Q000473:pathology / Q000601:surgery; D042442:Vascular Endothelial Growth Factors / Q000235:genetics
chemical_list: C515482:CCL22 protein, human; C515202:CXCL11 protein, human; D054422:Chemokine CCL22; D054371:Chemokine CXCL11; D018076:DNA, Complementary; D012333:RNA, Messenger; D042442:Vascular Endothelial Growth Factors