Electroacupuncture Ameliorates Scopolamine-Induced Dry Eye Disease in Mice by Restoring Lacrimal Gland Lipid Homeostasis and Reducing IL-1β/IL-18 Expression.

Dry eye disease (DED) can lead to severe eye discomfort, which manifests as dryness, pain and decreased vision, and significantly affects daily life. This study elucidated the effects of electroacupuncture (EA) intervention on DED and clarified its potential mechanisms through changes in lacrimal gland lipid metabolism and inflammation. A DED mouse model was established by repeated subcutaneous injections of scopolamine hydrobromide, followed by EA intervention. The therapeutic effects of EA intervention on DED were determined based on tear secretion volume (n = 10), corneal fluorescein staining scores (n = 10), corneal stromal (CS) damage (n = 6), and changes in corneal and lacrimal gland morphology (n = 10). Mechanistic endpoints included lacrimal gland lipidomic profiling by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) (n = 6) and assessment of IL-1β and IL-18 expression by immunohistochemistry (n = 6), western blotting (n = 3) and qRT-PCR (n = 6). EA increased tear secretion, reduced corneal fluorescein staining and ameliorated CS and lacrimal gland pathological alterations. Lipidomic analysis identified 81 metabolites, and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis highlighted arachidonic acid metabolism and inflammation-related pathways. EA reduced arachidonic acid and several downstream pro-inflammatory metabolites while partially restoring omega-3 polyunsaturated fatty acids (PUFAs) and their derivatives. EA also reduced lacrimal gland IL-1β and IL-18 expression at the protein and mRNA levels. These findings suggest that EA may ameliorate scopolamine-induced DED, at least in part, through modulation of lacrimal gland lipid homeostasis and suppression of inflammatory responses.