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Mechanisms of Mesenchymal Stem Cell-Derived Exosomes in Dry Eye Disease: From Inflammation Pathways to Therapeutic
Jiahuan Yi1, Fangfang Lu1, Yale Tian2
1Department of Ophthalmology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China, usc.edu.cn.
Abstract:
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.
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