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Regional Differences in Store-Operated Ca²⁺ Entry in the Epithelium of the Intact Human Lens

¹From the School of Biological Sciences, University of East Anglia, Norwich, United Kingdom; and ²Norfolk and Norwich University Hospital, Norwich, United Kingdom.

PURPOSE. An elevated level of Ca²⁺ is an important factor in cataract, yet precisely how Ca²⁺ enters the lens is unknown. Lens epithelial cells contain a range of G-protein–coupled receptors and receptor tyrosine kinases that induce increases in intracellular Ca²⁺. Receptor-associated Ca²⁺ influx is, therefore, likely to be an important route for Ca²⁺ influx to the lens. The authors investigated stimulated and passive Ca²⁺ influx in in situ human lens epithelium.

METHODS. Ca²⁺ changes in equatorial (E) and central anterior (CA) epithelial cells were monitored with the use of a Ca²⁺ indicator (Fluo4) and confocal microscopy. Gene expression was monitored by RT-PCR and immunoblotting.

RESULTS. Adenosine triphosphate (ATP) induced Ca²⁺ responses that were smaller in CA than E. Ca²⁺ store depletion, using ATP (100 µM) or thapsigargin (1 µM), revealed greater relative store capacity and Ca²⁺ influx in E. Ca²⁺ influx was blocked by La³⁺ (0.5 µM) in both regions. Unstimulated Ca²⁺ influx was greater in E than CA. Greater expression of Orai1 and STIM1 was detected in E than in CA.

CONCLUSIONS. Greater Ca²⁺ store capacity and Ca²⁺ influx in E compared with CA reflects underlying differences in proliferation and differentiation between the regions. The relatively small resting Ca²⁺ influx in CA epithelium suggests that store-operated Ca²⁺ entry (SOCE) is the main route of Ca²⁺ influx in these cells. Greater resting influx and SOCE in E cells suggests that these are a major route for Ca²⁺ influx into the lens. Increased expression of Orai1 and STIM1 in E could account for the differences in Ca²⁺ entry. Receptor activation will modulate Ca²⁺ influx, and inappropriate activity may contribute to cortical cataract.