Blue light pollution induces dry eye by damaging conjunctival stem cells through cAMP-PKA-Pax6 signaling pathway

Blue light exposure constitutes a risk factor for dry eye. The research explores the influence of conjunctival stem cells (CjSCs) by blue light, elucidating the pathogenesis of blue light-induced dry eye. Primary SD rat CjSCs and rats were irradiated with blue light at 460 nm. The impact of blue light illumination on both CjSCs and rats was examined, and RNA-sequencing (RNA-seq) identified the specific mechanisms. Additionally, blue light-irradiated rats and primary CjSCs were treated with Forskolin to validate the effects of the cAMP-PKA pathway on CjSCs differentiation and blue light-induced dry eye. Blue light exposure not only affected the stemness and proliferation of CjSCs, but also disturbed the differentiation by down-regulating the expression of Pax6. Mechanically, the cAMP-PKA signaling pathway was significantly inhibited following blue light emission. Reduced P-PKA expression affected Pax6 transcription, which in turn promoted abnormal differentiation of CjSCs. Moreover, Forskolin, a specific agonist of cAMP-PKA, effectively rescued the drawback of blue light irradiation on CjSCs. Blue light exposure results in abnormal differentiation in CjSCs through the down-regulation of the expression of Pax6 via the cAMP-PKA signaling pathway. The abnormal differentiation in CjSCs should be pursued as a novel target for protection against blue light-induced dry eye.