Proteome Analysis of Nasolacrimal Duct Lavage Fluid in Patients with Primary Acquired Nasolacrimal Duct Obstruction

Primary acquired nasolacrimal duct obstruction (PANDO) is a common cause of epiphora in adults, yet the biochemical environment within the nasolacrimal duct (NLD) remains poorly understood. This study aimed to characterize the proteomic composition of NLD lavage fluid and identify subtype-specific molecular features distinguishing membranous and mucinous obstruction. Paired tear and NLD lavage fluid (NLD-LF) samples were collected from patients undergoing dacryoendoscopic recanalization, and proteomic profiling was performed using LC–MS/MS. A total of 1345 proteins were identified in NLD-LF and 767 in tear fluid, revealing a distinct NLD-specific proteome. Although the membranous and mucinous subtypes shared broadly similar protein compositions, differentially expressed proteins highlighted divergent biochemical pathways. The membranous subtype showed enrichment of keratinization-related processes involving KRT1, KRT9, and KLK13, suggesting epithelial remodeling and cornification. In contrast, the mucinous subtype exhibited upregulation of proteins involved in lipid metabolism, carboxylic acid biosynthesis, and sulfur compound metabolism, including ALOX15B, LCAT, and GSTM4, indicating metabolic conditions that promote mucin–lipid interactions, glycan sulfation, and redox-dependent mucin cross-linking. These findings provide new insights into the protein composition of NLD lavage fluid and suggest molecular differences between the membranous and mucinous obstruction subtypes.