TRPV4 channel-mediated calcium signalling in human lens epithelium of cataract patients and healthy lens capsules.

PURPOSE: Transient receptor potential vanilloid 4 (TRPV4) channels are mechanosensitive ion channels implicated in Ca2+ signalling across various tissues, yet their functional role in human lens epithelial cells remains poorly understood. We aimed to investigate the contribution of TRPV4 to mechanically induced Ca2+ signalling in human anterior lens epithelium.

METHODS

Human anterior lens epithelial preparations were obtained from postoperative lens capsules, including both cataractous and non-cataractous samples. Using multicellular Ca2+ imaging, we analysed the spatiotemporal properties of intercellular Ca2+ waves following localised mechanical stimulation under control conditions and after pharmacological inhibition of TRPV4 with HC-067047.

RESULTS

Mechanical stimulation triggered radially propagating Ca2+ waves characterised by distance-dependent attenuation of amplitude and kinetics. TRPV4 inhibition significantly reduced wave propagation velocity and enhanced spatial signal decay, indicating a key role in maintaining efficient intercellular Ca2+ signal propagation. These effects were most pronounced in non-cataractous epithelium, while in cataractous lenses, they exhibited stage-dependent differences, suggesting remodelling of Ca2+ signalling pathways during disease progression. The observed intercellular Ca2+ wave propagation is consistent with gap junctional and paracrine signalling, while TRPV4 activity modulates its efficiency by shaping the initiating Ca2+ response.

CONCLUSION

TRPV4 channels contribute to both the efficiency and spatial extent of Ca2+ signalling in the lens epithelium. These findings identify TRPV4 as an important regulator of mechanically induced intercellular communication and a potential target for modulating lens function in health and disease.