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

Pathol Int. 2011 Sep;61(9):528-35. doi: 10.1111/j.1440-1827.2011.02695.x. Epub 2011 Aug 1.


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cell Polarity
  • Chemokine CCL22 / genetics
  • Chemokine CXCL11 / genetics
  • Choroid / pathology
  • Choroid / surgery
  • Choroidal Neovascularization / genetics
  • Choroidal Neovascularization / pathology*
  • Choroidal Neovascularization / surgery
  • DNA, Complementary / genetics
  • Female
  • Humans
  • Macrophage Activation / immunology*
  • Macrophages / cytology*
  • Macrophages / immunology
  • Macula Lutea / pathology*
  • Macular Degeneration / genetics
  • Macular Degeneration / pathology*
  • Macular Degeneration / surgery
  • Male
  • Microdissection
  • Middle Aged
  • Phenotype
  • Pilot Projects
  • RNA, Messenger / genetics
  • Retina / pathology
  • Retina / surgery
  • Vascular Endothelial Growth Factors / genetics


  • CCL22 protein, human
  • CXCL11 protein, human
  • Chemokine CCL22
  • Chemokine CXCL11
  • DNA, Complementary
  • RNA, Messenger
  • Vascular Endothelial Growth Factors