Gp91phox‐derived Reactive Oxygen Species/Urocortin 2/Corticotropin‐releasing Hormone Receptor Type 2 Play an Important Role in Long‐term Ultraviolet A Eye Irradiation‐induced Photoaging

Photoaging is induced by long‐term ultraviolet A (UVA) eye irradiation. However, the mechanism of skin damage due to UVA eye irradiation is still not well understood. In this study, we used C57BL/6j and gp91phox knockout (gp91phox^?/?) mice for the long‐term effects of UVA irradiation. The eye or dorsal skin of the mice was locally exposed to UVA for 12 months. The reactive oxygen species (ROS), gp91phox, corticotropin‐releasing hormone (CRH), urocortin 2, and CRH receptor (CRHR) type 1 and type 2 levels in the brain and mast cell tryptase and histamine levels in the dorsal skin all increased after UVA irradiation. The levels of CRH, urocortin 2, CRHR type 1 and type 2 in the brain also increased more after UVA eye irradiation than after UVA skin irradiation. Moreover, photoaging of the UVA eye irradiation mice was not induced following the administration of a ROS inhibitor in the brain. In addition, in gp91phox^?/? mice, photoaging by UVA eye irradiation was not induced. These results indicate that long‐term UVA eye irradiation led to increased gp91phox‐derived ROS in the brain and the increased expression of urocortin 2 and CRHR type 2, resulting in photoaging; however, further studies are needed to confirm these findings.