Mechanisms of Mesenchymal Stem Cell-Derived Exosomes in Dry Eye Disease: From Inflammation Pathways to Therapeutic Prospects.

Dry eye disease (DED) is a chronic ocular surface disorder triggered by tear film imbalance, in which inflammatory disruption of immune homeostasis constitutes the core pathological mechanism. Mesenchymal stem cell-derived exosomes (MSC-Exos) offer promising anti-inflammatory therapeutic potential through immune modulation, tissue repair, and their inherently low immunogenicity. This review elucidates MSC-Exos' molecular regulation of DED inflammation, demonstrating their suppression of the TLR4/NF-κB signaling axis, the IRAK1/TRAF6/NF-κB cascade reaction, the STAT3 transcriptional regulatory network, and the NLRP3 inflammasome activation pathway, while revealing a synergistic mechanism through which MSC-Exos ameliorate the ocular surface inflammatory microenvironment by modulating the Th17/Treg immune balance via the gut-eye axis and facilitating FBXW7-mediated ubiquitination degradation pathways. Despite this therapeutic potential, clinical translation is hampered by exosomal heterogeneity, difficulties in standardization, and suboptimal delivery efficiency and long-term efficacy. Future progress will require the integration of nanotechnology and gene editing to enhance therapeutic functionality, ultimately positioning MSC-Exos as precision biologics for DED.