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I. M. Wormstone, M. Johnston, L. J. Dawes, J. A. Maidment, L. Wang, L. M. Hodgkinson, J. Hadfield, J. R. Reddan; Histamine Stimulates Multiple Signalling Pathways in Human Lens Cells Leading to Accelerated Growth Rate. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1597.
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© ARVO (1962-2015); The Authors (2016-present)
Histamine is an important inflammatory molecule. Following injury to the eye, such as cataract surgery, levels are likely to rise and could contribute to the development of posterior capsule opacification. Consequently, we investigated the effect of histamine on signalling pathways and growth rates of human lens cells.
Histamine receptor gene expression in the native human lens and the human lens cell line FHL 124 was determined by gene array analysis. Calcium signalling was investigated through imaging of FURA-2 loaded cells while phosphorylation of ERK, p38 and JNK in response to histamine was assessed using the BIOPLEX suspended bead array system. Growth rate was assessed in FHL 124 cells by changes in protein level detected by coomassie blue dye extraction and 3H-thymidine incorporation. In addition, the human capsular bag model was employed; in this system, cell growth was measured as coverage of the central posterior capsule.
Analysis of array data from the human lens revealed only the H1-receptor sub type is detectable; this is exclusively expressed in the epithelial cell population. Moreover, this pattern of expression is conserved in the FHL 124 cell line. Application of histamine to FHL 124 cells produced a dose-dependent increase in intracellular calcium, with detectable responses observed from 1µM histamine. Addition of 100µM histamine induced significant elevation of phosphorylated ERK and P38; pJNK was also elevated, but this change was not significant. In each case, peak response was observed 10 minutes following stimulation. Addition of histamine (≥30µM) significantly stimulated FHL 124 cell growth. Moreover the rate of cell coverage of the posterior capsule in capsular bags was accelerated by 10µM histamine; this response was inhibited by 10µM triprolidine (H1-receptor antagonist).
The dominant histamine receptor present in lens epithelial cells is the H1 receptor sub-type. Activation of this receptor induces significant changes in calcium and MAPK signalling pathways. In addition, histamine stimulates an accelerated growth response that could contribute to PCO progression; therefore, histamine receptor antagonists could provide therapeutic benefit following cataract surgery.
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