OPN5 and TRPV4 subserve intrinsic photosensitivity in mouse corneal epithelium

AbstractThe ocular surface protects the eye from pathogens, mechanical impact and harmful radiation. Excessive exposure of corneal epithelial (CE) layers to ultraviolet B (UVB) photons compromises these protective functions and may be associated with inflammation, pain, vision loss and cancer. We investigated the mechanisms that translate corneal epithelial (CE) transduction of UVB photons into intracellular and inflammatory signaling. Optical imaging in dissociated CECs and intact CE sheets showed rapid, UVB-induced increases in intracellular calcium concentration [Ca2+]i that were partially reduced by the TRPV4 antagonist HC067047, removal of extracellular Ca2+ and knockdown of the Trpv4 gene, and obliterated by depletion of internal calcium stores. Knockdown of neuropsin and inhibition of phospholipase C signaling markedly reduced the amplitude of the evoked calcium signal. UVB photons promoted release of cytokines and chemokines that included interleukins, metalloproteinases and thymic stromal lymphopoietin (TSLP). CECs are thus intrinsically photosensitive, utilizing a rhabdomeric-like phototransduction pathway cou0led to cytokine release to alert trigeminal afferents and stromal keratocytes about the presence of harmful irradiation and protect the visual system from snow blindness, injury, vision loss and cancer.