Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 5843-5855 |
| Number of pages | 13 |
| Journal | Investigative Ophthalmology and Visual Science |
| Volume | 57 |
| Issue number | 14 |
| DOIs | |
| State | Published - Nov 1 2016 |
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Keywords
- Age-related macular degeneration
- Choriocapillaris
- Choroidal neovascularization
- Choroidal vasculature
- Macrophages
ASJC Scopus subject areas
- Ophthalmology
- Sensory Systems
- Cellular and Molecular Neuroscience
Cite this
Distribution and quantification of choroidal macrophages in human eyes with age-related macular degeneration. / McLeod, D. Scott; Bhutto, Imran; Edwards, Malia; Silver, Rachel E.; Seddon, Johanna M.; Lutty, Gerard Anthony.
In: Investigative Ophthalmology and Visual Science, Vol. 57, No. 14, 01.11.2016, p. 5843-5855.Research output: Contribution to journal › Article
}
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
AU - Silver, Rachel E.
AU - Seddon, Johanna M.
AU - Lutty, Gerard Anthony
PY - 2016/11/1
Y1 - 2016/11/1
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
UR - http://www.scopus.com/inward/record.url?scp=84994504816&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84994504816&partnerID=8YFLogxK
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 -