Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Internal Medicine, Howard University Hospital, Washington, DC, USA.
FASEB J. 2021 Feb;35(2):e21327. doi: 10.1096/fj.202002323R.
Recently, elongase of very long chain fatty acids-3 (ELOVL3) was demonstrated to play a pivotal role in physiology and biochemistry of the ocular surface by maintaining a proper balance in the lipid composition of meibum. The goal of this study was to further investigate the effects of ELOVL3 ablation in homozygous Elovl3-knockout mice (E3hom) in comparison with age and sex matched wild-type controls (E3wt). Slit lamp examination of the ocular surface of mice, and histological examination of their ocular tissues, highlighted a severe negative impact of Elovl3 inactivating mutation on the Meibomian glands (MG) and conjunctiva of mice. MG transcriptomes of the E3hom and E3wt mice were assessed and revealed a range of up- and downregulated genes related to lipid biosynthesis, inflammation, and stress response, compared with E3wt mice. Heat stage polarized light microscopy was used to assess melting characteristics of normal and abnormal meibum. The loss of Elovl3 led to a 8°C drop in the melting temperature of meibum in E3hom mice, and increased its fluidity. Also noted were the excessive accumulation of lipid material and tears around the eye and severe ocular inflammation, among other abnormalities.
最近，长链脂肪酸延长酶 3（ELOVL3）通过维持睑板腺油脂成分的适当平衡，在眼表面的生理学和生物化学中发挥着关键作用。本研究的目的是进一步研究与年龄和性别匹配的野生型对照（E3wt）相比，ELOVL3 缺失在纯合 Elovl3 敲除小鼠（E3hom）中的作用。对小鼠眼表面的裂隙灯检查和对其眼部组织的组织学检查突出表明，Elovl3 失活突变对小鼠的睑板腺（MG）和结膜有严重的负面影响。对 E3hom 和 E3wt 小鼠的 MG 转录组进行了评估，与 E3wt 小鼠相比，发现了一系列与脂质生物合成、炎症和应激反应相关的上调和下调基因。使用热台偏光显微镜评估了正常和异常睑板腺油脂的熔化特性。Elovl3 的缺失导致 E3hom 小鼠睑板腺油脂的熔化温度下降 8°C，流动性增加。还注意到眼睛周围的脂质物质和眼泪过度积聚以及严重的眼部炎症等异常。
