Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9057, USA.
The Graduate School of Biomedical Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390-9057, USA.
Int J Mol Sci. 2021 Feb 4;22(4):1583. doi: 10.3390/ijms22041583.
Previous studies on ablation of several key genes of meibogenesis related to fatty acid elongation, omega oxidation, and esterification into wax esters have demonstrated that inactivation of any of them led to predicted changes in the meibum lipid profiles and caused severe abnormalities in the ocular surface and Meibomian gland (MG) physiology and morphology. In this study, we evaluated the effects of ablation that were expected to cause depletion of the second largest class of Meibomian lipids (ML)-cholesteryl esters (CE)-in a mouse model. ML of the null mice were examined using liquid chromatography high-resolution mass spectrometry and compared with those of and wild-type mice. Complete suppression of CE biosynthesis and simultaneous accumulation of free cholesterol (Chl) were observed in null mice, while mutants had normal Chl and CE profiles. The total arrest of the CE biosynthesis in response to ablation transformed Chl into the dominant lipid in meibum accounting for at least 30% of all ML. The null mice had clear manifestations of dry eye and MG dysfunction. Enrichment of meibum with Chl and depletion of CE caused plugging of MG orifices, increased meibum rigidity and melting temperature, and led to a massive accumulation of lipid deposits around the eyes of -null mice. These findings illustrate the role of /SOAT1 in the lipid homeostasis and pathophysiology of MG.
先前的研究表明，对与脂肪酸伸长、ω 氧化和酯化生成蜡酯有关的几个眼板生成关键基因进行消融，会导致预测的类脂分泌物脂质谱发生变化，并导致眼表面和睑板腺（MG）生理和形态严重异常。在这项研究中，我们评估了在小鼠模型中预期会导致第二类最大的睑板分泌物（ML）-胆固醇酯（CE）耗竭的消融效果。使用液相色谱高分辨率质谱法检查了缺失型小鼠的 ML，并与 和野生型小鼠的 ML 进行了比较。在缺失型小鼠中观察到 CE 生物合成的完全抑制和游离胆固醇（Chl）的同时积累，而 突变体具有正常的 Chl 和 CE 谱。CE 生物合成的完全抑制导致 Chl 转化为类脂分泌物中的主要脂质，至少占所有 ML 的 30%。缺失型小鼠表现出明显的干眼和 MG 功能障碍。Chl 在类脂分泌物中的富集和 CE 的耗竭导致 MG 口堵塞、增加类脂分泌物的刚性和熔点，并导致 -null 小鼠眼睛周围大量脂质沉积。这些发现说明了 /SOAT1 在 MG 的脂质动态平衡和病理生理学中的作用。
