Therapeutic Potential of Umbilical Cord MSC-Derived Exosomes in a Severe Dry Eye Rat Model: Enhancing Corneal Protection and Modulating Inflammation

<b>Background/Objectives</b>: Dry eye disease (DED) is a multifactorial inflammatory disease that disrupts the ocular surface, causing tear film instability, epithelial damage, and chronic inflammation. Mesenchymal stem cell-derived exosomes (MSC-exos) are promising therapeutics with imm...

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Main Authors: Sze-Min Chan, Chris Tsai, Tai-Ping Lee, Zih-Rou Huang, Wei-Hsiang Huang, Chung-Tien Lin
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/5/1174
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Summary:<b>Background/Objectives</b>: Dry eye disease (DED) is a multifactorial inflammatory disease that disrupts the ocular surface, causing tear film instability, epithelial damage, and chronic inflammation. Mesenchymal stem cell-derived exosomes (MSC-exos) are promising therapeutics with immunomodulatory and regenerative properties. This study investigates the therapeutic effects of umbilical cord MSC-derived exosomes (UCMSC-exos) in a severe dry eye model, induced by a surgical resection of the infra-orbital (ILG) and extra-orbital lacrimal gland (ELG) in rats. <b>Methods</b>: Clinical evaluations, including tear volume measurement, slit lamp biomicroscopy, fluorescein staining, and spectral domain optical coherence tomography (SD-OCT), were performed to assess corneal neovascularization, corneal abrasion, and epithelial/stromal thickness. Histopathological analysis, immunohistochemistry, and mRNA gene expression were conducted to evaluate corneal tissue changes and inflammatory marker expression. <b>Results</b>: The results show that the treatment group exhibited significantly reduced corneal neovascularization compared to the control group (<i>p</i> = 0.030). During the first month, the Exo group also had a significantly lower corneal fluorescein staining area (<i>p</i> = 0.032), suggesting accelerated wound healing. SD-OCT analysis revealed that the corneal epithelial thickness in the treatment group was closer to normal levels compared to the control group (<i>p</i> = 0.02 and <i>p</i> = 0.006, respectively). UCMSC-exos treatment also modulated the expression of α-SMA and apoptosis in the cornea. Additionally, the gene expression of inflammatory cytokines (IL-1β and TNF-α) were downregulated. <b>Conclusions</b>: These findings suggest that MSC-exosome therapy offers a novel, cell-free regenerative approach for managing severe DED, modulating inflammatory response.
ISSN:2227-9059