Engineered CGRP Eye Drops Restore Tear Secretion via TRPM8-SSN Circuitry in a Postrefractive Surgery Mouse Model

Area of Science:

• Ophthalmology
• Neuroscience
• Molecular Biology

Background:

• Postrefractive surgery can cause dry eye due to corneal nerve damage.
• Sensory neuropeptides like calcitonin gene-related peptide (CGRP) play a role in ocular surface homeostasis.
• Understanding CGRP's role is vital for developing effective dry eye treatments.

Purpose of the Study:

• To investigate the role of CGRP in dry eye following corneal nerve severing in a mouse model.
• To evaluate the therapeutic potential of CGRP and an engineered CGRP (eCGRP) for postrefractive surgery dry eye.

Main Methods:

• Established mouse models of corneal nerve severing and photorefractive keratectomy (PRK).
• Assessed corneal sensitivity, nerve density, tear secretion, and epithelial integrity.
• Utilized immunofluorescence, RNA sequencing, and electrophysiology to analyze neural pathways (TRPM8-SSN).

Main Results:

• Corneal nerve severing reduced CGRP, leading to dry eye symptoms and nerve degeneration.
• CGRP administration (prophylactic and therapeutic) rescued dry eye.
• Topical eCGRP showed superior efficacy in increasing tear secretion and reducing inflammation without side effects, confirmed in the PRK model.

Conclusions:

• CGRP downregulation contributes to postrefractive surgery dry eye by impairing the TRPM8-SSN pathway.
• Engineered CGRP (eCGRP) offers a promising therapeutic strategy for preventing and treating this condition.