Calcitonin Gene-Related Peptide Ameliorates Experimental Dry Eye Disease

Purpose: Calcitonin gene-related peptide (CGRP) level is reduced in the tears of patients with dry eye disease (DED). The current study aims to investigate the expression and therapeutic potential of CGRP as topical eye drops in treating experimental DED. Methods: Human corneal epithelial cells (CECs) were cultured under hyperosmotic stress (HS) and the effects of CGRP on cell viability, proliferation, migration, and apoptosis were determined in vitro. The expression of CGRP in the cornea and trigeminal ganglion (TG) of desiccating stress-induced experimental DED mice was determined. CGRP or albumin control were topically applied thrice daily for two weeks in DED mice and DED parameters were assessed clinically. Cornea and conjunctiva were collected separately after treatment, and cell proliferation and tissue inflammation were determined using immunostaining and flow cytometry. Results: Experimental DED mice showed significantly reduced CGRP mRNA and protein expression in their cornea and TG. CGRP promoted proliferation and downregulated apoptosis, TNF-α, IL-1β, and IL-6 mRNA levels during HS in cultured CECs. Clinically, topical application of CGRP significantly decreased corneal fluorescein staining score, increased tear break-up time, and preserved corneal epithelium in DED mice. In the cornea, CGRP significantly promoted epithelial proliferation and reduced infiltrating CD45+ leukocytes, and TNF-α and IL-1β expression in vivo. CGRP treatment did not significantly affect the frequency of CD45+ leukocytes in the conjunctiva. Conclusions: Our data demonstrate that CGRP expression in the cornea and TG is downregulated in DED. Topical CGRP treatment ameliorates DED severity by promoting epithelial proliferation and suppressing inflammation in the cornea.