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Christopher Wanderling, Paulius V Kuprys, Sean Forte, Algis Grybauskas, Kevin Skuran, Alexandra Johnson, Zibute Zaparackas, Paul A Knepper; On the role of intermediate monocyte subtypes in POAG: Possible cause of disease propagation. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4518.
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Primary open-angle glaucoma (POAG) is a primary neuronal disease of the optic nerve without a definable cause. Our lab has previously identified an innate immune response elicited in treated trabecular meshwork cells. Monocytes, one of the main facilitators of the innate immune response, have been shown to be important in the maintenance of aqueous outflow and invasion of the optic nerve head in mice. Recently, monocytes have been divided into three subtypes: classical (CD14++/CD16-), intermediate (CD14++/CD16+), and nonclassical (CD14+/CD16++). Each of these subtypes has characteristically different functions. A relative change in the percentage of subtypes has been implicated in a variety of diseases (e.g. Eale’s disease, rheumatoid arthritis). The purpose of this study is to identify differences in monocyte subtypes between POAG patients and controls.
Blood samples from control (n=4), normal tension glaucoma (NTG; n=4), and POAG (n=3) patients were obtained in EDTA anticoagulant tubes. Centrifugation was used to isolate mononuclear cells. Cells were stained with anti-CD14-FITC (a co-receptor with Toll-like receptor 4 and MD-2 for the detection of lipopolysaccharide) and anti-CD16-PE-Cy5 (a low affinity Fc receptor). Appropriate isotype controls were used. Samples were then examined by flow cytometry.
A change in the intermediate monocyte population was found between controls, NTG, and POAG. The lowest proportion of intermediate monocytes was found in the controls (2.70%, n=4), followed by normal tension glaucoma (4.98%, n= 4) and POAG (6.42%, n=3). A significant difference was found between the control and POAG patient intermediate monocytes (P< 0.05). In addition, a statistical significance was found when comparing control and NTG patients versus POAG patients (P< 0.05).
Both NTG and POAG have an increase in the intermediate monocyte subtype, which is known for its proangiogenic capacity. The expansion of the intermediate population seems to suggest that this subtype is actively involved in the repair, removal, and propagation of the disease.
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