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CD163+ macrophages infiltrate axon bundles of postmortem optic nerves with glaucoma
Milica A Margeta1, Eleonora M Lad2, Alan D Proia2,3
1Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, 243 Charles Street, Boston, MA, 02114, USA. milica_margeta@meei.harvard.edu.
Purpose:
Prior research in animal models has shown that macrophages and microglia play an important role in pathogenesis of glaucoma, but the phenotype and distribution of macrophages in human glaucomatous tissue have not been sufficiently characterized.
Methods:
We analyzed H&E, CD68-, and CD163-immunostained slides from 25 formaldehyde-fixed, paraffin-embedded autopsy eyes: 12 control eyes and 13 eyes with glaucoma. The diagnosis of glaucoma was made based on a history of glaucoma as reported in the medical record and histological changes characteristic of glaucoma. Glaucoma cases and controls were matched in terms of age, sex, and race.
Results:
Qualitative analysis of the conventional outflow pathway and the optic nerve revealed that all eyes contained CD163+ cells but a negligible number of CD68+ cells. CD163+ macrophages infiltrated the trabecular meshwork and surrounded Schlemm's canal of normal eyes and eyes with glaucoma, but the pattern was variable and qualitatively similar between groups. In optic nerves of control eyes, CD163+ macrophages were present at low levels and restricted to septa between axon bundles. In glaucomatous optic nerves, the number of CD163+ cells was increased both qualitatively and quantitatively (glaucoma 5.1 ± 0.6 CD163+ cells/mm2, control 2.5 ± 0.3 CD163+ cells/mm2, p < 0.001), with CD163+ cells infiltrating axon bundles in cases of both mild and severe diseases.
Conclusions:
The increase in CD163+ cell number in eyes with mild and severe glaucoma is the first demonstration of macrophage infiltration in glaucomatous human optic nerves. This finding supports a role for macrophages in glaucoma pathogenesis and progression.
Insights
Macrophages, identified by CD163, infiltrate human optic nerves in glaucoma. Increased CD163+ cells in glaucomatous optic nerves suggest a role for these immune cells in glaucoma progression.
Area of Science:
- Ophthalmology
- Immunology
- Cell Biology
Background:
- Animal models indicate macrophages and microglia are key in glaucoma pathogenesis.
- Characterization of macrophage phenotype and distribution in human glaucomatous tissue is limited.
Purpose of the Study:
- To characterize the phenotype and distribution of macrophages in human glaucomatous ocular tissue.
- To investigate the role of macrophages in the pathogenesis and progression of human glaucoma.
Main Methods:
- Analysis of H&E, CD68, and CD163-immunostained autopsy eye slides from 12 control and 13 glaucoma cases.
- Matched controls for age, sex, and race.
- Qualitative and quantitative assessment of macrophage infiltration in the conventional outflow pathway and optic nerve.
Main Results:
- CD163+ macrophages were present in all eyes, while CD68+ cells were negligible.
- CD163+ macrophages infiltrated the trabecular meshwork and surrounded Schlemm's canal in both control and glaucoma eyes.
- A significant increase in CD163+ macrophages was observed in glaucomatous optic nerves compared to controls (5.1 vs. 2.5 cells/mm², p < 0.001), with infiltration into axon bundles.
Conclusions:
- This study provides the first evidence of macrophage infiltration in human glaucomatous optic nerves.
- The increased number of CD163+ cells in mild and severe glaucoma supports a role for macrophages in disease pathogenesis and progression.
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