Alteration in bone marrow derived macrophage and trabecular meshwork cell reactions under increased hydrostatic pressure
In the presented thesis, the influence of increased hydrostatic pressure (HP) and dexamethasone treatment on bone marrow derived macrophages (BMDMs) or human trabecular meshwork (HTM) cells was investigated. A pressure chamber system was used to culture cells at room pressure, 20 mmHg, or 60 mmHg. After culture at the different HPs for various time points (2 days or 7 days), cells were analyzed by immunofluorescence microscopy, flow cytometry, bioassay, enzyme-linked immunosorbent assay (ELISA). BMDMs cultured under increased HP (60 mmHg) for 24 or 48 hours showed increased pro-inflammatory reactions and pronounced M1 polarization. After exposure of BMDMs to higher HP for 1 week, macrophages shifted to an M2 polarization with wound healing reaction. Moreover, dexamethasone treatment of macrophages induced a pronounced M2 polarization after 48h and 7 days. This M2 polarization could be further enlarged by increased HP. Increased Arg-1/2 expression and activity upon increased HP or increased deposition of extracellular matrx (ECM) molecules after dexamethasone treatment may be related to the obstruction of the outflow pathway during the development of glaucoma and glucocorticoid (GC)-induced ocular hypertension (OHT)/glaucoma in uveitis. Similar to macrophages, HTM cells showed increased deposition of ECM proteins and an increased arginase (Arg)-1 expression and activity under higher pressure (60mmHg), which increased further by dexamethasone treatment. Modulation of the arginase and tumor necrosis factor (TNF)-α response under increase HP seem to play an important role in the function of both macrophages and HTM cells. The promoted inflammatory process, arginase expression/activity and deposition of ECM by higher pressure in macrophages or HTM cultures seem to be closely related to the pressure-induced IRI in the eye and can be responsible for the development and deterioration of OHT or secondary glaucoma in uveitis.
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