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Milica Margeta, Eleonora M Lad, Alan D Proia; Abundance of CD163+ macrophages/microglia in the optic nerves of human post-mortem eyes with glaucoma. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2546.
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© ARVO (1962-2015); The Authors (2016-present)
Prior studies have documented presence of macrophages in the conventional outflow pathway and microglia in the optic nerves of human autopsy eyes. It is not known whether these cells are “classically activated” M1 macrophages/microglia, which release proinflammatory destructive mediators, or non-classical, “alternatively activated” M2 cells, which are involved in phagocytosis and tissue repair.
We analyzed H&E, CD163 and CD68 immunostained slides from 25 formaldehyde-fixed, paraffin-embedded autopsy eyes: 12 control eyes and 13 eyes with glaucoma. CD163 is commonly used as a non-classical M2 macrophage marker, and CD68 as an M1 marker. The diagnosis of glaucoma was made based on reported history of glaucoma and use of IOP-lowering eyedrops, as well as histological changes characteristic of glaucoma. Glaucoma cases and controls were matched in terms of age, sex, and race.
Qualitative analysis revealed that all eyes contained a significant number of CD163+ cells but a negligible number of CD68+ cells in the structures critical for pathogenesis of glaucoma. CD163+ macrophages infiltrated the trabecular meshwork and surrounded the Schlemm’s canal of normal eyes and eyes with glaucoma, but the pattern was variable and qualitatively similar between groups. In the optic nerves of control eyes, CD163+ microglia/macrophages were present at low levels, especially in the area of the lamina cribrosa. In glaucomatous eyes, the number of CD163+ cells was significantly increased both qualitatively and quantitatively [percentage stained area 0.89% (SEM 0.13) in controls and 2.45% (SEM 0.35) in glaucoma cases; p=0.004].
Our results demonstrate that CD163+ cells are significantly increased in number in the optic nerves of eyes with glaucoma, suggesting that alternatively activated, M2 macrophages/microglia play a role in the pathogenesis of the disease. Since M2 macrophages and microglia have previously been shown to promote neuronal survival and regeneration, this raises the exciting possibility that they also may play a neuroprotective role in glaucoma.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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