Targeting α7 Nicotinic Acetylcholine Receptor for Modulating the Neuroinflammation of Dry Eye Disease Via Macrophages.

PURPOSE: Patients with dry eye disease (DED) often exhibit neurological abnormalities and may even suffer from neuropathic pain and pain-related anxiety or depression. The α-7 nicotinic acetylcholine receptor (α7nAChR) is a pivotal regulator in the anti-inflammatory pathway connecting the nervous and immune systems, Here, we investigate the potential of α7nAChR agonist as a novel treatment for DED.

METHODS

We induced DED model by unilateral excision of extraorbital lachrymal gland in C57/BL6 mice. After seven days of treatment, RNA sequencing was performed to identify differentially expressed genes in the cornea of lacrimal gland excision (LGE) mice. Quantitative polymerase chain reaction, Western blotting, and flow cytometry tests were carried out to elucidate neuroinflammation changes after α7nAChR activation. Corneal nerve abnormalities were assessed by corneal esthesiometry and immunofluorescence staining.

RESULTS

The activation of α7nAChR stimulates genes involved in immune-mediated inflammatory progression and neuroregulation, inhibits the expression of transient receptor potential vanilloid-1, reinstates corneal nerve density, and alleviates anxiety-like behaviors associated with severe DED. Furthermore, we demonstrated that α7nAChR agonist restored corneal nerve abnormality and alleviated inflammation response by down-regulating the proportion of CD86+ M1 macrophages (proinflammatory phenotypes).

CONCLUSIONS

Our findings underscore the activation of α7nAChR as a pioneering therapeutic approach for preserving corneal nerves balance and controlling inflammation in DED.