TY - JOUR
T1 - Distribution and quantification of choroidal macrophages in human eyes with age-related macular degeneration
AU - McLeod, D. Scott
AU - Bhutto, Imran
AU - Edwards, Malia M.
AU - Silver, Rachel E.
AU - Seddon, Johanna M.
AU - Lutty, Gerard A.
N1 - Funding Information:
The authors thank the eye donors and their relatives for their generosity. We also thank Mercedes B. Villalonga, BA, Tufts Medical Center, for assistance with organizing procurement of ocular tissue and for documentation of ocular history and AMD classification. Part of this study was presented at the International Society for Eye Research Meeting, San Francisco, California, July 20-24, 2014, and at the annual meeting of the Association for Research in Vision and Ophthalmology, Seattle, Washington, May 1-5, 2016.Supported by National Institutes of Health Grants EY-01765 (Wilmer), R01-EY016151 (GAL), and RO1 EY08552 (JMS), unrestricted funds from Research to Prevent Blindness (Wilmer and Tufts Medical Center), the Macular Degeneration Research Fund, Tufts Medical Center, Tufts University School of Medicine (Boston, MA, USA) (JMS), the Arnold and Mabel Beckman Foundation (GAL and JMS), the Foundation Fighting Blindness (GAL and JMS), Bright Focus Foundation (IB), and the Altsheler Durell Foundation. GAL received an RPB Senior Scientific Investigator Award in 2008.
Publisher Copyright:
© 2016, Association for Research in Vision and Ophthalmology Inc. All rights reserved.
PY - 2016/11
Y1 - 2016/11
N2 - PURPOSE. Increasing evidence suggests a role for macrophages in the pathogenesis of agerelated macular degeneration (AMD). This study examined choroidal macrophages and their activation in postmortem eyes from subjects with and without AMD. METHODS. Choroids were incubated with anti-ionized calcium-binding adapter molecule 1 (anti-IBA1) to label macrophages, anti-human leukocyte antigen-antigen D-related (anti-HLADR) as a macrophage activation marker, and Ulex europaeus agglutinin lectin to label blood vessels. Whole mounts were imaged using confocal microscopy. IBA1-and HLA-DR–positive (activated) cells were counted in submacula, paramacula, and nonmacula, and cell volume and sphericity were determined using computer-assisted image analysis. RESULTS. In aged control eyes, the mean number of submacular IBA1+ and HLA-DR+ macrophages was 433/mm2 and 152/mm2, respectively. In early AMD eyes, there was a significant increase in IBA1+ and HLA-DR+ cells in submacula compared to those in controls (P = 0.0015 and P = 0.008, respectively). In eyes with neovascular AMD, there were significantly more HLA-DR+ cells associated with submacular choroidal neovascularization (P = 0.001). Mean cell volume was significantly lower (P ≤ 0.02), and sphericity was significantly higher (P ≤ 0.005) in all AMD groups compared to controls. CONCLUSIONS. The average number of IBA1+ macrophages in submacular and paramacular choroid was significantly higher in early/intermediate AMD compared to that in aged controls. HLA-DR+ submacular macrophages were significantly increased in all stages of AMD, and they were significantly more round and smaller in size in the submacular AMD choroid, suggesting their activation. These findings support the concept that AMD is an inflammatory disease.
AB - PURPOSE. Increasing evidence suggests a role for macrophages in the pathogenesis of agerelated macular degeneration (AMD). This study examined choroidal macrophages and their activation in postmortem eyes from subjects with and without AMD. METHODS. Choroids were incubated with anti-ionized calcium-binding adapter molecule 1 (anti-IBA1) to label macrophages, anti-human leukocyte antigen-antigen D-related (anti-HLADR) as a macrophage activation marker, and Ulex europaeus agglutinin lectin to label blood vessels. Whole mounts were imaged using confocal microscopy. IBA1-and HLA-DR–positive (activated) cells were counted in submacula, paramacula, and nonmacula, and cell volume and sphericity were determined using computer-assisted image analysis. RESULTS. In aged control eyes, the mean number of submacular IBA1+ and HLA-DR+ macrophages was 433/mm2 and 152/mm2, respectively. In early AMD eyes, there was a significant increase in IBA1+ and HLA-DR+ cells in submacula compared to those in controls (P = 0.0015 and P = 0.008, respectively). In eyes with neovascular AMD, there were significantly more HLA-DR+ cells associated with submacular choroidal neovascularization (P = 0.001). Mean cell volume was significantly lower (P ≤ 0.02), and sphericity was significantly higher (P ≤ 0.005) in all AMD groups compared to controls. CONCLUSIONS. The average number of IBA1+ macrophages in submacular and paramacular choroid was significantly higher in early/intermediate AMD compared to that in aged controls. HLA-DR+ submacular macrophages were significantly increased in all stages of AMD, and they were significantly more round and smaller in size in the submacular AMD choroid, suggesting their activation. These findings support the concept that AMD is an inflammatory disease.
KW - Age-related macular degeneration
KW - Choriocapillaris
KW - Choroidal neovascularization
KW - Choroidal vasculature
KW - Macrophages
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U2 - 10.1167/iovs.16-20049
DO - 10.1167/iovs.16-20049
M3 - Article
C2 - 27802514
AN - SCOPUS:84994504816
VL - 57
SP - 5843
EP - 5855
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
SN - 0146-0404
IS - 14
ER -