PURPOSE: To investigate intrinsic phototransduction in the corneal epithelium and its role in intracellular and inflammatory signaling. METHODS: 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 RESULTS: 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 [Ca CONCLUSIONS: 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.