Department of Ophthalmology, University of Szeged, Szeged, Hungary.
Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary.
Invest Ophthalmol Vis Sci. 2024 May 1;65(5):30. doi: 10.1167/iovs.65.5.30.
Earlier reports highlighted the predominant presence of aquaporin 4 (AQP4) in the duct cells of rabbit lacrimal glands (LGs). Whereas significant alterations in AQP4 mRNA levels have been observed in experimental dry eye and during pregnancy, the impact of AQP4 in LG ductal fluid production remains unclear. In our recent work, the role of AQP4 in LG ductal fluid secretion was investigated utilizing wild type (WT) and AQP4 knock out (KO) mice.
Tear production was assessed in both WT and KO animals. Immunostaining was used to identify AQP4 protein. Duct segments were harvested from LGs of WT and KO mice. Fluid secretion and filtration permeability (Pf) were quantified using video-microscopy. Ductal tear production, elicited by a cell-permeable cAMP analogue (8-bromo cAMP), carbachol, vasoactive intestinal peptide (VIP), and phenylephrine (PHE), were assessed in both WT and KO ducts.
A higher expression of AQP4 protein was noted in the duct cells from WT mice when compared to acinar cells. Pf did not show notable alterations between WT and AQP4 KO ducts. Carbachol elicited comparable secretory responses in ducts from both WT and KO animals. However, 8-bromo cAMP, VIP, and PHE stimulation resulted in decreased secretion in ducts from AQP4 KO LGs.
Our findings underscore the functional relevance of AQP4 in the fluid production of mouse LG ducts. AQP4 seems to play different roles in fluid secretions elicited by different secretagogues. Specifically, cAMP-mediated, and adrenergic agonist-related secretions were reduced in AQP4 KO ducts.
早期的报告强调水通道蛋白 4（AQP4）在兔泪腺（LG）的导管细胞中占优势。尽管在实验性干眼症和怀孕期间观察到 AQP4 mRNA 水平的显著变化，但 AQP4 在 LG 导管液体产生中的作用仍不清楚。在我们最近的工作中，利用野生型（WT）和 AQP4 敲除（KO）小鼠研究了 AQP4 在 LG 导管液体分泌中的作用。
评估 WT 和 KO 动物的泪液产生。免疫染色用于鉴定 AQP4 蛋白。从 WT 和 KO 小鼠的 LG 中收获导管段。使用视频显微镜定量测量流体分泌和过滤渗透率（Pf）。在 WT 和 KO 导管中评估细胞渗透性 cAMP 类似物（8-溴 cAMP）、卡巴胆碱、血管活性肠肽（VIP）和苯肾上腺素（PHE）诱导的导管泪液产生。
与腺细胞相比，WT 小鼠导管细胞中 AQP4 蛋白表达更高。WT 和 AQP4 KO 导管之间 Pf 没有明显变化。卡巴胆碱在 WT 和 KO 动物的导管中引起相似的分泌反应。然而，8-溴 cAMP、VIP 和 PHE 刺激导致 AQP4 KO LG 导管中的分泌减少。
我们的发现强调了 AQP4 在小鼠 LG 导管液体产生中的功能相关性。AQP4 在不同的刺激物引起的液体分泌中似乎发挥不同的作用。具体而言，cAMP 介导的和肾上腺素激动剂相关的分泌在 AQP4 KO 导管中减少。
