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I Kaiserman, D Kraus, A Fendyur, J Frucht-Pery, R Rahamimoff; Intercellular Calcium Signals in Cataractous Lens Epithelium . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3538.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The pathogenesis of cataract is still subject to debate. However, during the last decade several studies have implicated intra-cellular calcium as an important factor in cataractogenesis. The purpose of this study was to characterize inter-cellular calcium signaling in cataractous lens epithelium, impairment of which might be the basis of cataract formation. Methods: We used confocal laser scanning microscopy to monitor (at 100Hz) local intracellular calcium levels in primary cultures (4-6 days old) of cataractous human lens cells loaded with a calcium-sensitive fluorophore (Fluo4). Forty-one cells were mechanically stimulated and calcium dynamics were monitored in their neighbors.Time series, auto-correlation and cross-correlation analyses were used to characterize the calcium signals. To investigate the physiological basis of these signals, cultures were pretreated with Ryanodine and Thapsigargin. Results: We looked at the inter- and intra-cellular calcium signaling in mechanically stimulated cataractous lens epithelium. All stimulated cells and their 3-4 adjacent tiers of neighbors responded with a significant calcium elevation upon mechanical stimulation. This large calcium response subsided in 40-90 sec. We noted a large difference between the fast propagation of calcium signals inside cells and the delayed transmission of the signal to their neighbors. Calcium signal transmission was delayed by 2.7sec (±1.1SD) between the stimulated cell and its adjacent neighbor, 5.2sec (±2.0) between first and second neighbor, and 4.8sec (±0.5) between second and third neighbor. The initiation of the calcium wave in the neighboring cells was usually in the center, not adjacent to the activating cell, suggesting that a different messenger other than calcium transmits the inter-cellular signal. Occasionally, several activation foci were noted in one cell. Thapsigargin (1µM) and Ryanodine (100µM) blocked the inter-cellular signals, suggesting they are based on intra-cellular calcium stores. This was supported by the fact that removing extracellular calcium did not affect inter-cellular communication. Conclusion: In human cataractous lens epithelium there is inter-cellular calcium communication which is based on intra-cellular calcium stores. These signals are transmitted by an inter-cellular messenger other than calcium.
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