Eye Institute of Xiamen University, Xiamen, China; School of Medicine, Xiamen University, Xiamen, China; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen University, Xiamen, China.
Eye Institute of Xiamen University, Xiamen, China; School of Medicine, Xiamen University, Xiamen, China; Xiang'an Hospital of Xiamen University, Xiamen, China; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen University, Xiamen, China.
Am J Pathol. 2020 Dec;190(12):2387-2402. doi: 10.1016/j.ajpath.2020.09.002. Epub 2020 Sep 11.
The lacrimal gland is critical for maintaining the homeostasis of the ocular surface microenvironment through secreting aqueous tears in mammals. Many systemic diseases such as Sjögren syndrome, rheumatoid arthritis, and diabetes can alter the lacrimal gland function, eventually resulting in aqueous tear-deficient dry eye. Here, a high-fat diet (HFD) experimental mouse model was used to clarify how hyperlipidemia affects lacrimal gland function. Aqueous tear secretion fell about 50% after 1 month on a HFD. Lipid droplets accumulated in the matrix and acinar cells of the lacrimal gland after this period, along with changes in the lipid metabolism, changes in gene expression levels, and disruption of fatty acid oxidative activity. Immune cell infiltration and rises in the gene expression levels of the inflammation-related cytokines Il1β, Tnfα, Tsg6, Il10, Mmp2, and Mmp9 were found. HFD also induced mitochondrial hypermegasoma, increased apoptosis, and decreased lacrimal gland acinar cell proliferation. Replacement of the HFD with the standard diet partially reversed pathologic changes in the lacrimal gland. Similarly, supplementing the HFD with fenofibrate also partially reversed the inhibited tear secretion and reduced lipid accumulation, inflammation, and oxidative stress levels. The authors conclude that a HFD induces pathophysiological changes and functional decompensation of the lacrimal gland. Therefore, ingestion of a HFD may be a causative factor of dry eye disease.
泪腺通过在哺乳动物中分泌水样泪液对于维持眼表微环境的稳态至关重要。许多全身性疾病，如干燥综合征、类风湿关节炎和糖尿病，都可以改变泪腺的功能，最终导致水样液缺乏性干眼症。在这里，使用高脂肪饮食（HFD）实验小鼠模型来阐明高脂血症如何影响泪腺功能。在 HFD 饮食 1 个月后，水样泪液分泌量下降了约 50%。在此期间，脂质滴在泪腺的基质和腺泡细胞中积累，伴随着脂质代谢的改变、基因表达水平的变化以及脂肪酸氧化活性的破坏。免疫细胞浸润和与炎症相关的细胞因子 Il1β、Tnfα、Tsg6、Il10、Mmp2 和 Mmp9 的基因表达水平升高。HFD 还诱导了线粒体的超巨体形成，增加了细胞凋亡，并减少了泪腺腺泡细胞的增殖。用标准饮食替代 HFD 部分逆转了泪腺的病理变化。同样，在用非诺贝特补充 HFD 时，也部分逆转了抑制的泪液分泌以及减少的脂质积累、炎症和氧化应激水平。作者得出结论，HFD 引起了泪腺的病理生理变化和功能失代偿。因此，摄入 HFD 可能是干眼症的一个致病因素。
