Cataract Progression Associated with Modifications in Calcium Signaling in Human Lens Epithelia as Studied by Mechanical Stimulation

Ca²⁺ homeostasis and signaling disturbances are associated with lens pathophysiology and are involved in cataract formation. Here, we explored the spatiotemporal changes in Ca²⁺ signaling in lens epithelial cells (LECs) upon local mechanical stimulation, to better understand the LECs' intercellular communication and its association with cataractogenesis. We were interested in if the progression of the cataract affects the Ca²⁺ signaling and if modifications of the Ca²⁺ homeostasis in LECs are associated with different cataract types. Experiments were done on the human postoperative anterior lens capsule (LC) preparations consisting of the monolayer of LECs on the basement membrane. Our findings revealed that the Ca²⁺ signal spreads radially from the stimulation point and that the amplitude of Ca²⁺ transients decreases with increasing distance. It is noteworthy that a comparison of signaling characteristics with respect to the degree of cataract progression revealed that, in LCs from more developed cataracts, the Ca²⁺ wave propagates faster and the amplitudes of Ca²⁺ signals are lower, while their durations are longer. No differences were identified when comparing LCs with regard to the cataract type. Moreover, experiments with Apyrase have revealed that the Ca²⁺ signals are not affected by ATP-dependent paracrine communication. Our results indicated that cataract progression is associated with modifications in Ca²⁺ signaling in LECs, suggesting the functional importance of altered Ca²⁺ signaling of LECs in cataractogenesis.