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D. Wallace, M. Irnaten, R. Barry, A. Duff, N. Docherty, B. Quill, A. Clark, C. O'Brien; Abnormal Calcium Homeostasis in Glaucomatous Lamina Cribrosa Cells. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6104.
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The pathological features of glaucoma include cupping and pallor of the optic nerve head (ONH) and characteristic visual field loss. Cupping of the ONH is associated with compression and collapse of the lamina cribrosa (LC) connective tissue. Calcium is a key regulator of diverse cellular functions and consequently intracellular Ca2+ ([Ca2+]i) levels are tightly regulated. Raised [Ca2+]i is a feature of numerous neurodegenerative and cardiac conditions. The purpose of this study was to examine the [Ca2+]i levels and calcium homeostasis mechanisms in ONH glial fibrillary acidic protein negative lamina cribrosa cells.
Calcium entry, stores, extrusion and downstream pathways were assessed using patch-clamp, calcium imaging, flow-cytometry, Real-Time PCR and Western blot (+/- specific inhibitors).
Compared with LC cells from normal donors, basal and stretch-induced Ca2+-dependent maxi-K+ channel activity, free [Ca2+]i levels, and phosphorylated PKCα are elevated in LC cells from glaucoma patients. In the glaucoma LC cells, the expression of the critical calcium regulators plasma membrane Ca2+ ATPase (PMCA) and sodium-calcium exchanger (NCX) are reduced, while the intracellular sarco-endoplasmic reticulum Ca2+-ATPase reuptake store expression is increased. Under basal conditions no difference was noted in the functional activity of the L-type and Store Operated Ca2+ entry channels, however, under stretch conditions maxi-K+ current amplitudes were significantly greater in GLC cells following treatment with L-type (verapamil) and Store Operated Ca2+ channels (2-APB) blockers.
Glaucoma LC cells show abnormalities in Ca2+ entry, re-uptake, extrusion and downstream signaling pathways associated with elevation of cytosolic [Ca2+]i. The dysfunction in Ca2+ regulation by these cells may provide a stage on which to examine the role of Ca2+ dysregulation in the long-term remodelling activity of ONH glia.
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