Abstract

Introduction Human amniotic epithelial cell-derived extracellular vesicles (hAEC-EVs) have shown therapeutic potential in corneal injury repair; however, the underlying molecular mechanisms, particularly those related to extracellular matrix (ECM) remodeling, remain incompletely understood. Methods A proteomic and bioinformatic strategy was applied to analyze ECM-related molecular alterations in corneal tissues following alkali injury and hAEC-EV treatment. Differentially expressed ECM-related genes were identified and subjected to pathway enrichment, protein–protein interaction, and immune infiltration analyses. To enhance experimental rigor, key findings were validated at both the transcript and protein levels using quantitative real-time PCR and Western blotting. In addition, in vitro functional assays were performed to assess the effects of hAEC-EVs on corneal epithelial and stromal cell proliferation and migration. Results hAEC-EV treatment significantly upregulated ECM-stabilizing molecules, including A2M, LAMA1, and VIT, while downregulating the injury- and inflammation-associated protease CTSB at both mRNA and protein levels. Enrichment analyses revealed that hAEC-EVs modulate ECM–receptor interaction pathways and cell–ECM communication. Functional assays confirmed that hAEC-EVs directly enhance the proliferation and migration of human corneal epithelial cells and human corneal stromal cells. Immune infiltration analysis further suggested that hAEC-EVs reshape the corneal immune microenvironment toward a repair-permissive state. Conclusion Through integrated proteomic, bioinformatic, protein-level validation, and functional analyses, this study demonstrates that hAEC-EVs promote corneal repair by coordinating ECM remodeling, regulating key signaling networks, and modulating immune responses, providing mechanistic support for their therapeutic application