TRPV1 channels facilitate axonal degeneration of corneal sensory nerves in dry eye

Am J Pathol. 2024 Feb 5:S0002-9440(24)00047-6. doi: 10.1016/j.ajpath.2024.01.015. Online ahead of print.ABSTRACTCorneal nerve impairment contributes significantly to dry eye disease (DED) symptoms and is thought to be secondary to corneal epithelial damage. Transient receptor potential vanilloid-1 (TRPV1) channels abound in corneal nerve fibers and respond to inflammation-derived ligands, which increase in DED. TRPV1 overactivation promotes axonal degeneration in vitro but whether it participates in DED-associated corneal nerve dysfunction is unknown. To explore this, DED was surgically induced in wild-type and TRPV1-knockout (Trpv1KO) mice, which developed comparable corneal epithelial damage and reduced tear secretion. However, corneal mechanosensitivity decreased progressively only in wild-type DED mice. Sensitivity to capsaicin (TRPV1 agonist) increased in wild-type DED mice, and consistently, only this strain displayed DED-induced pain signs. Wild-type DED mice exhibited nerve degeneration throughout the corneal epithelium whereas Trpv1KO DED mice only developed a reduction in the most superficial nerve endings that failed to propagate to the deeper subbasal corneal nerves. Pharmacological TRPV1 blockade reproduced these findings in wild-type DED mice while CD4+ T cells from both strains were equally pathogenic when transferred, ruling out a T cell-mediated effect of TRPV1 deficiency. The data show that ocular desiccation triggers superficial corneal nerve damage in DED ...

Source: Am J Pathol - February 7, 2024 Category: Pathology Authors: Manuela Pizzano Alexia Vereertbrugghen Agostina Cernutto Florencia Sabbione Irene A Keitelman Carolina M Shiromizu Douglas Vera Aguilar Federico Fuentes Mirta N Giordano Anal ía S Trevani Jerem ías G Galletti Source Type: research