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

Abstract

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.

From Isles of Königsberg to Islets of Langerhans: Examining the Function of the Endocrine Pancreas Through Network Science

“…Multicellular recordings of membrane potential or intracellular calcium concentration are typically used as input signals. Network principles have thus been used to elucidate the connectivity patterns in neurons ( 40 – 44 ), astrocytes ( 45 ), pituitary endocrine cells ( 46 , 47 ), lens epithelium cells ( 48 , 49 ), hepatocytes ( 50 ), mammary epithelium cells ( 51 ), endothelial cells ( 52 ), and pancreatic acinar cells ( 53 ). Network analyses were introduced to the islet community a decade ago and are increasingly seen as a valuable tool to examine and quantify collective activity patterns in the pancreatic islets of Langerhans ( 18 , 54 – 69 ).…”

Bilateral hypocalcaemic cataracts due to idiopathic parathyroid insufficiency: A case report

“…The following consequences were observed: crystal fiber swelling, rupture, crystal protein denaturation, decomposition and caused cataract[ 13 , 14 ]. Disturbed calcium homeostasis can cause lens opacity through related mechanisms, such as abnormal differentiation of lens epithelial cells (LECs) into fibrocytes, increased migration of LECs into the posterior capsule, lens protein clustering and calcium channel inactivation[ 15 - 17 ]. In this case, we observed that the lens presented bilateral and symmetrical punctate opacity in the posterior subcapsular cortex together with radial opacity in the peripheral cortex.…”

The protective effect of pomegranate peel aqueous extract on selenite‐induced cataract in rats

“…Changes in the metabolism of the lens epithelium caused by oxidative stress impair Ca 2 + homeostasis and signaling. This event leads to calcium accumulation and calpain protease activation, which finally results in proteolytic processing of the β‐crystallins and lens opacification (Gosak et al, 2021; Maddirala et al, 2017; Tewari et al, 2019). Recent studies have indicated that the application of compounds with antioxidant properties can prevent oxidation‐related cataractogenesis (Maddirala et al, 2017; Tsai et al, 2019).…”