Substance P/neurokinin-1 receptor pathway blockade ameliorates limbal stem cell deficiency by modulating mTOR pathway and preventing cell senescence.

ABSTRACT: Severe ocular surface diseases can lead to limbal stem cell deficiency (LSCD), which is accompanied by defective healing. We aimed to evaluate the role of the substance P (SP)/neurokinin-1 receptor (NK1R) pathway in corneal epithelium wound healing in a pre-clinical model of LSCD. SP ablation or NK1R blockade significantly increased epithelial wound healing (p < 0.001) and corneal transparency (p < 0.001), compared with wild type (WT). In addition, a reduced number of infiltrating goblet and conjunctival cells (p < 0.05) and increased number of epithelial stem cells (p < 0.01), which also expressed NK1R, was observed. The mammalian target of rapamycin (mTOR) pathway was significantly inhibited (p < 0.05) and expression of γH2AX was significantly reduced (p < 0.05) after SP ablation. These

SUBMITTER: Lasagni Vitar R 

PROVIDER: S-EPMC9023781 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature