Corneal epithelial homeostasis (CEH) is essential for preserving ocular surface integrity and vision. While mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have been widely studied in ocular repair, the role of nerve-specific EVs remains poorly defined.

In this study, we investigated extracellular vesicles directly from corneal trigeminal nerves (TgV1-EVs) and their regulatory effects on corneal epithelial cells (CECs).
TgV1-EVs were isolated and characterized via Cryo-EM, Nanosight, ExoView, and Western blotting.

In vitro assays revealed that TgV1-EVs enhance CEC proliferation, differentiation, and barrier function, while in vivo subconjunctival injections promoted accelerated corneal epithelial wound healing. RNA-seq analysis on epithelial cells treated with neuronal EVs further identified over 2,400 differentially expressed genes linked to transcriptional reprogramming, metabolic adaptation, and stress responses.
These findings highlight the therapeutic potential of neuronal EVs in modulating corneal homeostasis and underscore their relevance as novel mediators of epithelial-neuronal communication in ocular surface health.