Abstract
Purpose :
In this study, we explored the therapeutic efficacy of Mesenchymal stromal cells -derived extracellular vesicles (MSC-EVs) in a mouse model of dry eye disease (DED) and assessed its ability to modulate immune responses and promote tissue repair in dry eye disease.
Methods :
DED was induced in female C57BL/6 mice by exposure to controlled environment chamber and subcutaneous injection of 0.5mg/0.2mL scopolamine hydrobromide four times per day for 14 days. Mice were grouped and treated with either MSC-EVs or PBS eye drops for comparison purposes. Samples of cornea, conjunctiva and draining lymph nodes were collected after treatment. Dendritic cells (DCs) were detected by immunofluorescence and flow cytometric analysis to assess its number and the expression of MHC-II and CD86. Th17 cells were detected by flow cytometric analysis to evaluate the antigen-presenting function of DCs. RT-PCR was performed to determine the mRNA expression of inflammatory cytokines in cornea and conjunctiva. In vitro, human corneal epithelial cells (HCEC) were cultured in hyperosmotic media and treated with MSC-EVs. Then cell viability was assessed by CCK8, and expression of inflammatory cytokines was detected by RT-PCR.
Results :
MSC-EVs-treated mice presented more tear production (P<0.05) and lower corneal fluorescein staining scores (P<0.05). DED upregulated the number of DCs and their maturation level, and treatment with MSC-EVs effectively reduced the number of DCs (P<0.05) and suppressed the expression of MHC-II (P<0.01) and CD86 (P<0.05). Reduction of Th17 cells was also observed in cornea and draining lymph nodes. Compared with untreated control group, expression of inflammatory cytokines was downregulated in cornea and conjunctiva of MSC-EVs-treated mice. In vitro, MSC-EVs protected HCECs against loss of cell viability induced by hyperosmotic stress. MSC-EVs also reduced the expression of inflammatory cytokines, including TNF-α, IL-1β, IFN-γ and IL-6.
Conclusions :
The results of our study revealed the role of MSC-EVs in regulating DC functions and promoting tissue regeneration in DED mice. MSC-EVs hold a great promise as a novel treatment method for DED and other ocular surface diseases.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.