Restoring key neuropeptides protects against infection after corneal nerve loss

When corneal sensory nerves are damaged, tear production decreases and key protective neuropeptides are reduced, making the eye more susceptible to bacterial infection, according to a study that found replacing these neuropeptides can restore defenses and reduce the risk of infection.

Researchers used a combination of subconjunctival and topical bupivacaine in mice to achieve localized, long-lasting nerve reduction, cutting corneal nerve density by about 50% without damaging the epithelium.

This nerve loss led to a 56% drop in tear production and significant decreases in substance P and calcitonin gene-related peptide (CGRP).  Lower neuropeptide levels were linked to greater bacterial adhesion, including a 20% rise for Pseudomonas aeruginosa and an 18% increase for Staphylococcus aureus.

Researchers noted that replacing substance P or CGRP restored normal neuropeptide levels, and adding CGRP specifically reduced bacterial adhesion. The model could help advance research into conditions like diabetic keratopathy and neurotrophic keratitis, as well as guide strategies for infection prevention and neuroprotective therapies.

Reference
Datta A, Orallo GK, Nelson N. Corneal sensory nerve loss induced by repeated subconjunctival and topical bupivacaine disrupts tear secretion and enhances bacterial adhesion via neuropeptide modulation. PLoS One. 2025;20(8):e0329112. doi: 10.1371/journal.pone.0329112. PMID: 40758689; PMCID: PMC12321116.