Liu Yang, Kam Wendy R, Sullivan David A
Schepens Eye Research Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA.
Cornea. 2016 Aug;35(8):1122-6. doi: 10.1097/ICO.0000000000000874.
Oral supplementation with omega 3 (ω-3) and/or 6 (ω-6) fatty acids (FAs) has been reported to alleviate the signs and symptoms of dry eye disease and to improve the expressibility and quality of meibum, in patients with meibomian gland dysfunction. We tested our hypothesis that these FA effects may reflect a direct FA action on human meibomian gland epithelial cells.
Immortalized human meibomian gland epithelial cells (IHMGECs) were cultured with ω-3, ω-6, or both FAs together for up to 7 days in the presence or absence of serum. After FA exposure, cells were analyzed for lipid expression, lysosome content, and proliferative ability.
Our research shows that ω-3 and ω-6 stimulate the accumulation of small neutral lipid-containing vesicles, but not lysosomes, in IHMGECs. This vesicular effect was associated with a 2.4- to 3.7-fold increase in the cellular content of triglycerides after ω-3 and ω-6 treatment, respectively. The combination of both FAs together also enhanced triglyceride levels. Of interest, culture of IHMGECs with ω-3 and azithromycin, a known inducer of IHMGEC differentiation, led to a significantly greater amount of total neutral lipids, relative to that found with azithromycin alone. Cellular exposure to the FAs did not alter the expression of free or esterified cholesterol, or phospholipids. Further, these FAs, alone or together, prevented the proliferation of IHMGECs in serum-free, but not serum-containing, media.
Our findings support our hypothesis and demonstrate that ω-3 and ω-6 can act directly on IHMGECs to influence the quality and quantity of intracellular lipids.
据报道,口服补充ω-3和/或ω-6脂肪酸(FAs)可缓解干眼疾病的体征和症状,并改善睑板腺功能障碍患者睑脂的可挤压性和质量。我们验证了这样一个假设,即这些脂肪酸的作用可能反映了脂肪酸对人睑板腺上皮细胞的直接作用。
在有或无血清存在的情况下,将永生化人睑板腺上皮细胞(IHMGECs)与ω-3、ω-6或两种脂肪酸一起培养长达7天。脂肪酸处理后,分析细胞的脂质表达、溶酶体含量和增殖能力。
我们的研究表明,ω-3和ω-6可刺激IHMGECs中含中性脂质的小囊泡的积累,但不刺激溶酶体的积累。这种囊泡效应分别与ω-3和ω-6处理后细胞内甘油三酯含量增加2.4至3.7倍有关。两种脂肪酸联合使用也可提高甘油三酯水平。有趣的是,将IHMGECs与ω-3和阿奇霉素(一种已知的IHMGEC分化诱导剂)一起培养,相对于单独使用阿奇霉素,可导致总中性脂质的量显著增加。细胞暴露于这些脂肪酸不会改变游离或酯化胆固醇或磷脂的表达。此外,这些脂肪酸单独或联合使用可在无血清但含血清的培养基中阻止IHMGECs的增殖。
我们的研究结果支持了我们的假设,并证明ω-3和ω-6可直接作用于IHMGECs,影响细胞内脂质的质量和数量。