The role of TRPV1 in corneal wound healing under a thyroxine-induced TAO-like condition

Thyroid-associated ophthalmopathy (TAO) is an autoimmune orbital disorder associated with proptosis, ocular surface exposure, and corneal complications that may impair corneal repair. Transient receptor potential vanilloid 1 (TRPV1) is a calcium-permeable stress sensor involved in epithelial repair, inflammation, and stromal remodeling; however, its role in corneal wound healing under TAO-like ocular surface conditions remains unclear. In this study, a thyroxine (T4)-induced TAO-like condition was established in rats, followed by standardized alkali corneal injury to evaluate healing responses under this condition. Rats received topical H89 (20 μM), a protein kinase A (PKA) inhibitor, or saline for 17 days. Corneal healing was evaluated by fluorescein staining, anterior-segment optical coherence tomography, histology, immunohistochemistry for p-PKA, TRPV1, p-PI3K, p-AKT, p-CREB, MPO, and α-SMA, and quantitative PCR for IL-1β and TRPV1. Rats with the TAO-like condition exhibited marked exophthalmos and showed delayed epithelial closure with increased corneal opacity and edema after injury. TRPV1 expression was increased in the basal epithelium and stroma, accompanied by enhanced MPO and α-SMA expression. Topical H89 was associated with improved epithelial healing, reduced inflammation and fibrosis, and lower IL-1β and TRPV1 mRNA expression. These changes were accompanied by altered expression of PKA/TRPV1-related signaling molecules. Collectively, these findings suggest that TRPV1-associated signaling is involved in inflammatory and fibrotic responses during corneal wound healing under TAO-like ocular surface conditions, and that pharmacologic modulation with H89 may help improve corneal repair in this setting.