Exploring the Therapeutic Potential of Salivary Exosomes in Corneal Epithelial Wound Healing.

PURPOSE: This study aimed to evaluate the therapeutic potential of salivary exosomes (SEs) in corneal epithelial wound healing by assessing their effects on wound closure, cellular function, and molecular mechanisms in both in vivo and in vitro models. METHODS: Corneal epithelial wounds were induced in C57BL/6J mice and treated with topical SEs (10 µg/eye) twice daily. Wound closure was monitored using fluorescein staining. In vitro, primary human corneal epithelial cells (HCECs) and human limbal epithelial cells (HLECs) were treated with SEs (0, 5, and 25 µg/mL) to assess migration, proliferation, and mitochondrial function. Western blot and immunohistochemistry were used to evaluate key molecular markers, including integrin α6, integrin β4, thrombospondin-1 (TSP1), and transforming growth factor-β1 (TGF-β1). RESULTS: SE treatment significantly accelerated corneal wound closure in vivo. In vitro, SEs enhanced HCEC and HLEC migration, proliferation, and mitochondrial function. SEs upregulated integrin α6, integrin β4, and TSP1 expression in both wounded corneas and cultured HCECs. TGF-β1 levels were transiently increased in exosome-treated corneas but returned to baseline as healing progressed. Mitochondrial stress assays revealed that SEs enhanced oxidative phosphorylation in HCECs and HLECs. CONCLUSIONS: SEs promote corneal epithelial wound healing by enhancing cellular migration, proliferation, and mitochondrial function while modulating key molecular pathways. These findings suggest that SEs represent a novel therapeutic strategy for corneal injury, warranting further investigation into their mechanisms and clinical applications.