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

• Type of Material: Article
• Authors: Xiaoguang Cao, National Eye Institute; Defen Shen, National Eye Institute; Mrinali M. Patel, National Eye Institute; Jingsheng Tuo, National Eye Institute; T. Mark Johnson, National Retina Institute; Timothy W Olsen, Emory University; Chi-Chao Chan, National Eye Institute
• Language: English
• Date: 2011-09-01
• Publisher: WILEY-BLACKWELL
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 US Government. Pathology International © 2011 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd.
• Final Published Version (URL): http://dx.doi.org/10.1111/j.1440-1827.2011.02695.x
• Title of Journal or Parent Work: Pathology International
• Volume: 61
• Issue: 9
• Start Page: 528
• End Page: 535
• Grant/Funding Information: The NEI Intramural Research program supported the study.
• Keywords: Science & Technology; chemokine; EXPRESSION; Life Sciences & Biomedicine; ANGIOGENESIS; BRUCHS MEMBRANE; PHENOTYPE; M1 macrophage; CHOROIDAL NEOVASCULARIZATION; INVOLVEMENT; age-related macular degeneration (AMD); INFLAMMATION; Pathology; choroidal neovascularization; SYSTEM; GROWTH; M2 macrophage; ACTIVATION
• Research Categories: Health Sciences, Pathology; Health Sciences, Opthamology

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.