253 Opsins and Cryptochrome photoreceptors mediate blue light stimulatory effect on hair growth

The therapeutic approach of photobiomodulation shows encouraging efficacy in hair loss treatment: more than 20 light-based devices have been safety-cleared to market by the FDA for the hair growth management. Yet lack of knowledge of the complexity of the molecular pathways that can be modulated by light hampers further progress in this field. The purpose of this study was to investigate the role of a range of photoreceptors as possible targets for superior light-based therapies for hair re-growth. We have previously reported 1) the spatio-temporal expression of Cryptochrome 1, Opsins 2 and 3, with absorption bands in the blue-to-green region, in the human hair follicle, and 2) that treatment with 3.2 Jxcm-2 of 453 nm blue light prolongs anagen phase in hair follicle ex vivo. In this study, we continued investigating the functional role of these photoreceptors and their potential to mediate the effects of blue light using the primary outer root sheath (ORS) cells. The siRNA-mediated inhibition of either CRY1 or OPN3 in the ORS keratinocytes resulted in the reduced proliferation. Transcriptomic analysis showed that either CRY1 or OPN3 siRNA causes alterations in the expression of genes controlling proliferation and apoptosis. For example, CRY1 siRNA suppressed the expression of CDK6, PLEK2, TMBIM6, and KDELR1, while the expression of ULBP1, PAK2, FSTL1 and UBR5 was downregulated following OPN3 siRNA. The link between CRY1 and CDK6 was also confirmed in the hair follicle ex vivo model. Treatment with blue light stimulated CRY1 protein synthesis in both nuclear and cytoplasmic fractions of the ORS cells. In addition, 3,2 Jxcm-2 blue light significantly promoted metabolic activity and proliferation of the ORS in vitro that was abrogated by OPN3 knockdown. Taken together, our data suggest that 453 nm blue light at low radiant exposure exerts a positive effect on hair growth, potentially via interaction with CRY1 and OPN3.