Neuropsin, TRPV4 and intracellular calcium mediate intrinsic photosensitivity in corneal epithelial cells

To investigate intrinsic phototransduction in the corneal epithelium and its role in intracellular and inflammatory signaling.

Optical imaging in isolated corneal epithelial cells (CECs) and debrided epithelia was combined with molecular, biochemical, pharmacological assays and gene deletion studies to track UVB-induced calcium signaling and release of cytokines, chemokines and matrix remodeling enzymes. Results from wild type mouse CECs were compared to data obtained from Opn5^-/- and Trpv4^-/- cells.

UVB stimuli and TRPV4 activity induced epithelial release of IL-1β, IL-17, matrix metalloproteinases MMP-3/MMP-9, and thymic stromal lymphopoietin (TSLP). UVB stimuli evoked [Ca²⁺]_i elevations in dissociated mouse CECs that were partially reduced by inhibition of TRPV4 channels, Trpv4 knockdown and replacement of control saline with Ca²⁺-free saline. UVB-induced Ca²⁺ responses were significantly suppressed by OPN5 deletion and by inhibition of phospholipase C signaling, and responses were abrogated in cells with depleted intracellular Ca²⁺ stores.

Mammalian CECs are intrinsically and constitutively photosensitive. UVB photons are transduced by neuropsin, phospholipase C and CICR signaling, with mouse but not human CE transduction exhibiting a UVB-sensitive TRPV4 component. TRPV4 activity and UVB transduction are linked to cell-autonomous release of proinflammatory, matrix remodeling and nociceptive interleukins and MMPS. TRPV4-induced cytokine release may contribute to the pain induced by mechanical injury of the cornea and CEC photosensing may alert and protect the visual system from ultraviolet B (UVB) radiation -induced snow blindness, injury, vision loss and cancer.