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Amol Sura, Baoying Liu, Zhiyu Li, Susan Hannes, Siamon Gordon, Robert B Nussenblatt; Expression of MSR-1—a Class-A Macrophage Scavenger Receptor—May Be Altered in Ocular Sarcoidosis. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):854.
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© ARVO (1962-2015); The Authors (2016-present)
Ocular sarcoidosis is a multisystem, idiopathic disorder characterized by noncaseating granulomas in affected tissues including the eye. Granulomas arise from the transformation and reorganization of macrophages into epithelioid cells. The role that macrophages play in ocular inflammation, however, is less clear. In this present study we aimed to investigate the relationship between a macrophage scavenger receptor, MSR-1, and ocular sarcoidosis.
Human peripheral blood mononuclear cells were isolated from sarcoid patients and healthy controls using a Ficoll gradient centrifugation protocol. Monocytes were isolated from PBMCs using CD14+ magnetic separation beads (Miltenyi). RNA sequencing (Illumina) was used to study the transcriptome profiling of monoctyes from sarcoid patients, when compared to age and race matched controls. Quantitative real-time PCR (qPCR) was used to confirm RNAseq findings. For animal studies, Class-A scavenger receptor (SR-A) knockout mice and their wild type controls on a C57BL/6 background were immunized with LPS (100 μg) to induce endotoxin-induced uveitis (EIU). Anterior chamber taps for leukocyte cell count were performed at 24 h and 48 h after immunization.
RNA Sequencing (n=3 controls, n=4 patients) revealed a 1.49 ± .370 fold increase in MSR-1 RNA expression in sarcoid patients compared to healthy controls (p=.007). Quantitative RT-PCR (n=8 controls, n=11 patients) of MSR-1 RNA expression showed a non-significant increase in MSR-1 expression (95% CI: .821 ± 2.00) in sarcoid patients compared to controls. Mouse studies revealed that at 48 h, mice without EIU (n=5) had no cell filtration, SR-A (+) mice with EIU (n=5) had an average infiltration of 49 cells/μl, and SR-A (-) mice with EIU (n=5) had an average infiltration of 28 cells/μl.
Our data to date suggest that changes in MSR-1 expression may affect ocular inflammation. In affected patients, we found altered levels of MSR-1—a Class-A macrophage scavenger receptor (SR-A) known to play an important role in atherosclerotic inflammation and murine choroidal neovascularization. The decreased cell infiltration in SR-A knockout mice with uveitis—as well as the central role of macrophages in inflammatory eye diseases and granuloma formation—provide plausible connections between MSR-1 and the macrophage-mediated inflammatory response.
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