ABSTRACT
The prevalence of Light-emitting diodes (LEDs) has exposed us to an excessive amount of blue light (BL) which causes various ophthalmic diseases. Previous studies have shown that conjunctiva is vulnerable to BL. In this study, we aimed to investigate the underlying mechanism of BL-induced injury in conjunctiva. We placed C57BL/6 mice and human conjunctival epithelial cell lines (HCECs) under BL (440 nm ± 15 nm, 0.2 mW/cm2) to establish a BL injury model in vivo and in vitro. Immunohistochemistry and MDA assay were used to identify lipid peroxidation (LPO) in vivo. HE staining was applied to detect morphological damage of conjunctival epithelium. DCFH-DA, C11-BODIPY 581/591, Calcein-AM, and FeRhoNox™-1 probes were performed to identify ferroptosis levels in vitro. Real-time qPCR and Western blotting techniques were employed to uncover signaling pathways of blue light-induced ferroptosis. Our findings demonstrated that BL affected tear film instability and induced conjunctival epithelium injury in vivo. Ferrostatin-1 significantly alleviated blue light-induced ferroptosis in vivo and in vitro. BL downregulates the levels of solute carrier family 7 member 11 (SLC7A11), Ferritin heavy chain (FTH1), and glutathione peroxidase (GPX4) by inhibiting the activation and translocation of the Signal transducer and activator of transcription 3 (STAT3) from inducing Fe2+ burst, ROS and LPO accumulation, ultimately resulting in ferroptosis. This study will offer new insight into BL-induced conjunctival injury and LED-induced dry eye.
Subject(s)
Conjunctiva , Ferroptosis , Light , Mice, Inbred C57BL , Phospholipid Hydroperoxide Glutathione Peroxidase , STAT3 Transcription Factor , Animals , Conjunctiva/metabolism , Conjunctiva/radiation effects , Conjunctiva/pathology , Mice , Ferroptosis/radiation effects , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Humans , STAT3 Transcription Factor/metabolism , Amino Acid Transport System y+/metabolism , Amino Acid Transport System y+/genetics , Lipid Peroxidation/radiation effects , Cell Line , Epithelium/radiation effects , Epithelium/metabolism , Epithelium/pathology , Signal Transduction/radiation effects , Epithelial Cells/metabolism , Epithelial Cells/radiation effects , Epithelial Cells/pathology , Reactive Oxygen Species/metabolism , Phenylenediamines/pharmacology , Blue Light , CyclohexylaminesABSTRACT
Acquired corneal diseases such as dry eye disease (DED), keratitis and corneal alkali burns are significant contributors to vision impairment worldwide, and more effective and innovative therapies are urgently needed. The Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway plays an indispensable role in cell metabolism, inflammation and the immune response. Studies have shown that regulators of this pathway are extensively expressed in the cornea, inducing significant activation of JAK/STAT3 signaling in specific acquired corneal diseases. The activation of JAK/STAT3 signaling contributes to various pathophysiological processes in the cornea, including inflammation, neovascularization, fibrosis, and wound healing. In the context of DED, the hypertonic environment activates JAK/STAT3 signaling to stimulate corneal inflammation. Inflammation and injury progression in infectious keratitis can also be modulated by JAK/STAT3 signaling. Furthermore, JAK/STAT3 signaling is involved in every stage of corneal repair after alkali burns, including acute inflammation, angiogenesis and fibrosis. Treatments modulating JAK/STAT3 signaling have shown promising results in attenuating corneal damage, indicating its potential as a novel therapeutic target. Thus, this review emphasizes the multiple roles of the JAK/STAT3 signaling pathway in common acquired corneal disorders and summarizes the current achievements of JAK/STAT3-targeting therapy to provide new insights into future applications.
