Conclusions
Our data suggest a novel mechanism by which UCNV induces bilateral ferroptosis through the VIP/Hif1a/TfR1 pathway, which might be a promising therapeutic target for DES-induced by corneal refractive surgeries.
Methods
BALB/c mice were randomly divided into sham, unilateral corneal nerve cutting (UCNV) + saline, UCNV + vasoactive intestinal peptide (VIP), and UCNV + ferrostatin-1 (Fer-1, inhibitor of ferroptosis) groups. Corneal lissamine green dye and tear volume were measured before and two weeks after the surgery in all groups. Lacrimal glands were collected for secretory function testing, RNA sequencing, ferroptosis verification, and inflammatory factor detection.
Purpose
Dry eye syndrome (DES) is a prevalent postoperative complication after myopic corneal refractive surgeries and the main cause of postoperative dissatisfaction. Although great efforts have been made in recent decades, the molecular mechanism of postoperative DES remains poorly understood. Here, we used a series of bioinformatics approaches and experimental
Results
UCNV significantly induced bilateral decreases in tear secretion. Inhibition of the maturation and release of secretory vesicles was observed in bilateral lacrimal glands. More importantly, UCNV induced ferroptosis in bilateral lacrimal glands. Furthermore, UCNV significantly decreased VIP, a neural transmitter, in bilateral lacrimal glands, which increased Hif1a, the dominant transcription factor of transferrin receptor protein 1 (TfR1). Supplementary VIP inhibited ferroptosis, which decreased the inflammatory reaction and promoted the maturation and release of secretory vesicles. Supplementary VIP and Fer-1 improved tear secretion. Conclusions: Our data suggest a novel mechanism by which UCNV induces bilateral ferroptosis through the VIP/Hif1a/TfR1 pathway, which might be a promising therapeutic target for DES-induced by corneal refractive surgeries.