Obstruction of the Tear Drainage Altered Lacrimal Gland Structure and Function

Purpose: Orbital glands and drainage conduits are two distinct entities that constitute the lacrimal apparatus system, the malfunction of which leads to a range of ocular surface disorders. Despite the close functional relationship, how the two parts interact under pathophysiological conditions has not been directly tested. The study aims to investigate the lacrimal gland (LG) structural and functional changes upon the drainage system obstruction, thus, testing their function link. Methods: Dacryocystectomy was performed in C57BL/6 mice to create a surgical model for tear duct (TD) obstruction (STDOB). Prickle1 mutant line with congenital nasolacrimal duct dysplasia serves as a genetic model for TD obstruction (GTDOB). Alterations of the LG and the ocular surface in tear duct obstruction mice were examined. Results: STDOB and GTDOB mice showed similar ocular surface phenotypes, including epiphora, corneal epithelial defects, and conjunctival goblet cell abnormalities. At the molecular and cellular levels, aberrant secretory vesicle fusion of the LG acinar cells was observed with altered expression and localization of Rab3d, Vamp8, and Snap23, which function in membrane fusion. LG secretion was also altered in that lactoferrin, lipocalin2, and lysozyme expression were increased in both LG and tears. Furthermore, STDOB and GTDOB mice exhibited similar LG transcription profiles. Conclusions: Physical obstruction of tear drainage in STDOB or GTDOB mice leads to LG dysfunction, suggesting a long-distance interaction between the tear drainage conduits and the LG. We propose that various components of the lacrimal apparatus should be considered an integral unit in diagnosing and treating ocular surface diseases.