Abstract
Background
Corneal alkali burns can cause persistent inflammation and corneal neovascularization. In this study, we aimed to determine whether applying radiation-treated umbilical cord mesenchymal stem cells (UCMSCs) to the ocular surface via high oxygen-permeable hydrogel lenses has an effect on corneal alkali burns and to further investigate the underlying molecular mechanisms involved.
Methods
After the rabbit corneal burn model was established, the rabbits were randomly divided into the untreated group, the blank lens group, the radiation-treated UCMSC lens group, and the UCMSC I.V. group. Then, we measured corneal inflammation, neovascularization and corneal injury repair via slit lamp microscopy, captured anterior segment optical coherence tomography (AS-OCT), and performed hematoxylin-eosin staining. Moreover, corneas from the blank lens group and the radiation-treated UCMSC lens group were subjected to transcriptome gene sequencing, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and quantitative reverse transcription-polymerase chain reaction (qRT‒PCR).
Results
Compared with those in the other experimental groups, radiation-treated UCMSC lenses significantly decreased corneal inflammation and neovascularization and promoted the repair of corneal injury. Suppression of the T helper 17 (Th17) cell differentiation pathway plays a role in the therapeutic effect of radiation-treated UCMSC lenses. Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) revealed that the expression of interleukin (IL)-17 in corneas treated with radiation-treated UCMSC lenses was lower than that in corneas treated with blank lenses, and radiation-treated UCMSC lenses exhibited greater expression of IL-4 and signal transducer and activator of transcription 1 (STAT1), while the expression of cluster of differentiation-3G (CD3G), a linker for the activation of T cells (LAT), IL-6, IL-1B, CC chemokine receptor 6 (CCR6) and IL-23 exhibited the opposite effects (all P < 0.05).
Conclusions
Irradiated umbilical cord mesenchymal stem cell-coated high oxygen-permeable hydrogel lenses on the ocular surface inhibited corneal angiogenesis and inflammation and promoted the repair of corneal injury. The downregulation of Th17 cell differentiation might be responsible for these effects.