Decreased Levels of CGRP, SP Associated With Dry Eye Disease

Levels of tear calcitonin gene-related peptide (CGRP) and substance P (SP) were decreased in patients with dry eye disease (DED), indicating that there could be a relationship between tear neuropeptides and ocular neurosensory function. Meaningful correlations were found between decreased CGRP and SP levels and clinical symptoms of DED, according to a study published in Annals of Medicine.¹

DED is characterized by tears not being able to fully lubricate the eyes, either through not producing enough tears or through the eye producing tears of poor quality.² Inflammation can be a cause of the pain associated with the condition. Neuropeptides can be secreted due to stimuli or injuries from pathogens while also playing a role in regulating inflammation and can be mediators in regulation of immune cells. This study aimed to evaluate the levels of neuropeptides in the tears of patients living with DED as well as assess what the clinical associations with the severity of the disease.

All patients for this study were recruited from the Eye and Ear, Nose, and Throat Hospital located in Shanghai, China. Patients were excluded if they had a history of other ophthalmic diseases, a history of ocular medication use, or a recent ophthalmic surgery within the past 6 months. All participants had their first noninvasive breakup time (NIBUT-1^st), mean noninvasive breakup time (NIBUT-avg), corneal fluorescein staining (CFS) score, and tear meniscus height (TMH) collected. The Ocular Surface Disease Index was used to determine the severity of DED. Enzyme-linked immunosorbent assay kits were used to analyze and quantify the neuropeptides in the tear fluid of the participants. Visualization of corneal nerves was conducted using laser.

Patients with dry eye disease had lower levels of neuropeptides in their tears | Image credit: lenblr - stock.adobe.com

There were 12 healthy volunteers and 16 patients with DED included in this study with respective mean (SD) ages of 39.8 (13.4) years and 42.4 (11.5) years. There were 23 women and 5 men across the 2 groups.

Patients with DED had a significant decrease in mean tear levels of CGRP (5.4 [2.9] ng/mL vs 9.2 [2.2] ng/mL) when compared with the healthy controls. This association also seen with SP, with patients with DED having significantly lower mean tear levels of SP (18.4 [8.4] ng/mL vs 31.6 [12.0] ng/mL). Negative correlations were found between the concentration of CGRP and CFS scores, whereas positive correlations were found between NIBUT-1^st and NIBUT-avg and the tear CGRP levels. Positive correlations were also found between SP and NIBUT-1^st and NIBUT-avg. Patients with severe DED were found to have significantly decreased levels of CGRP when compared with patients with mild DED.

The researchers concluded that decreased levels of CGRP were associated with tear secretion and the severity of DED.

“These findings provide a foundation for further exploration of the potential utility of neuropeptides as therapeutic targets and diagnostic biomarkers…This opens up promising avenues for their application in both treatment and diagnostic contexts,” the authors wrote.

References

1. Zhang Y, Zhang H, Zhu X. Tear neuropeptides are associated with clinical symptoms and signs of dry eye patients. Ann Med. Published online January 17, 2025. doi:10.1080/07853890.2025.2451194
2. Mayo Clinic Staff. Dry eyes. Mayo Clinic. September 23, 2022. Accessed January 20, 2025. https://www.mayoclinic.org/diseases-conditions/dry-eyes/symptoms-causes/syc-20371863