The ocular surface · 2024
Neuropsin, TRPV4 and intracellular calcium mediate intrinsic photosensitivity in corneal epithelial cells.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Lapajne Luka, Lakk Monika, Rudzitis Christopher N, Vemaraju Shruti, Lang Richard A, Hawlina Marko, Križaj David
Аннотация
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-/- and Trpv4-/- cells.
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 [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.
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.
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-/- and Trpv4-/- cells.
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 [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.
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.