State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
Invest Ophthalmol Vis Sci. 2023 Jul 3;64(10):13. doi: 10.1167/iovs.64.10.13.
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.
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.
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.
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.
眼眶腺和引流管是构成泪器系统的两个不同实体，它们的功能障碍会导致一系列眼表面疾病。尽管它们之间存在密切的功能关系，但在病理生理条件下，这两个部分如何相互作用尚未得到直接验证。本研究旨在研究泪腺（LG）在引流系统阻塞时的结构和功能变化，从而检验它们的功能联系。
在 C57BL/6 小鼠中进行泪囊切除术，以建立泪管（TD）阻塞的手术模型（STDOB）。Prickle1 突变系具有先天性鼻泪管发育不良，作为 TD 阻塞的遗传模型（GTDOB）。检查泪管阻塞小鼠 LG 和眼表面的变化。
STDOB 和 GTDOB 小鼠表现出相似的眼表面表型，包括溢泪、角膜上皮缺损和结膜杯状细胞异常。在分子和细胞水平上，观察到 LG 腺泡细胞的异常分泌小泡融合，Rab3d、Vamp8 和 Snap23 的表达和定位发生改变，这些蛋白在膜融合中起作用。LG 分泌也发生改变，乳铁蛋白、脂钙蛋白 2 和溶菌酶的表达在 LG 和泪液中均增加。此外，STDOB 和 GTDOB 小鼠表现出相似的 LG 转录谱。
STDOB 或 GTDOB 小鼠的泪液引流物理阻塞导致 LG 功能障碍，提示泪液引流管和 LG 之间存在远距离相互作用。我们提出，应将各种泪器系统的组成部分视为诊断和治疗眼表面疾病的一个整体单元。
