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Physiological effects of inactivation and the roles of Elovl3 /ELOVL3 in maintaining ocular homeostasis
The FASEB Journal ( IF 4.4 ) Pub Date : 2021-01-17 , DOI: 10.1096/fj.202002323r
Amber Wilkerson 1 , Nita Bhat 1, 2 , Hoang Quoc Hai Pham 1, 3 , Seher Yuksel 1 , Igor Butovich 1, 4
Affiliation  

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.

中文翻译:

Elovl3 / ELOVL3失活的生理效应以及在维持眼稳态中的作用

最近,超长链脂肪酸延长酶 3 (ELOVL3) 被证明通过维持睑脂脂质组成的适当平衡,在眼表的生理学和生物化学中发挥关键作用。本研究的目的是进一步研究 ELOVL3 敲除对纯合 Elovl3 敲除小鼠 (E3hom) 与年龄和性别匹配的野生型对照 (E3wt) 的影响。对小鼠眼表的裂隙灯检查及其眼组织的组织学检查强调了 Elovl3 失活突变对小鼠睑板腺 (MG) 和结膜的严重负面影响。对 E3hom 和 E3wt 小鼠的 MG 转录组进行了评估,发现与 E3wt 小鼠相比,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正常和异常睑脂的熔化特征。Elovl3的缺失导致E3hom小鼠睑脂的熔化温度下降8°C,并增加其流动性。还注意到眼​​睛周围脂质物质和泪液的过度积累以及严重的眼部炎症等异常情况。
更新日期:2021-01-17
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