Umbilical mesenchymal stem cells attenuates corneal fibrosis induced by fungal keratitis through the TGFβ1/Smad2 signaling pathway
Abstract Background: Fungal keratitis (FK) is eye microbial infection disease which can leads to severe corneal blindness. Corneal scar formation is one of the major complications of fungal keratitis and is closely related to prognosis. The aim of the current investigation was to evaluate the anti-fibrosis effect of human umbilical cord mesenchymal stem cells (uMSCs) in FK model and further to explore underlying mechanisms. Methods: FK mice model was made by corneal epithelial scratching and F. solani inoculation. The C57BL/6J mice were randomly divided into four groups, including control group, FK group, vehicleinj FK group and uMSCsinj FK group. After injury, antifungal drug natamycin eye drops were used topically to FK mice eyes 6 times per day for 7 days to inhibit fungi growth. Mice received repeated subconjunctival injection of uMSCs or veichle for 3 times including the 1d, 4d and 7d after wounding. At 14d, 21d and 28d post-injury, clinical observation, histological examination, second harmonic generation, immunofluoresence staining and molecular assays were performed. Results: The uMSCs topical administration reduced corneal scar formation and corneal opacity, accompanying with decreased corneal thickness and inflammatory cell infiltration, following down-regulated fibrotic-related factors α-SMA, TGFβ1, CTGF, and COLⅠ and finally inhibited phosphorylation of TGFβ1/Smad2 signaling pathway, which indicating the potential anti-fibrotic and protective effect of human uMSCs against FK-induced corneal fibrosis. Conclusion: Human uMSCs can evidently inhibit corneal fibrosis after FK wounding through TGFβ1/Smad2 signaling pathway regulation. Keywords: Fungal keratitis, corneal fibrosis, umbilical cord mesenchymal stem cells