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眼表面边界润滑剂黏蛋白的转录、翻译和功能。

Transcription, translation, and function of lubricin, a boundary lubricant, at the ocular surface.

机构信息

Faculty of Kinesiology, Human Performance Laboratory Schulich School of Engineering, University of Calgary, Calgary, Alberta, Canada.

出版信息

JAMA Ophthalmol. 2013 Jun;131(6):766-76. doi: 10.1001/jamaophthalmol.2013.2385.

Abstract

IMPORTANCE

Lubricin may be an important barrier to the development of corneal and conjunctival epitheliopathies that may occur in dry eye disease and contact lens wear.

OBJECTIVE

To test the hypotheses that lubricin (ie, proteoglycan 4 [PRG4 ]), a boundary lubricant, is produced by ocular surface epithelia and acts to protect the cornea and conjunctiva against significant shear forces generated during an eyelid blink and that lubricin deficiency increases shear stress on the ocular surface and promotes corneal damage.

DESIGN, SETTING, AND PARTICIPANTS: Human, porcine, and mouse tissues and cells were processed for molecular biological, immunohistochemical, and tribological studies, and wild-type and PRG4 knockout mice were evaluated for corneal damage.

RESULTS

Our findings demonstrate that lubricin is transcribed and translated by corneal and conjunctival epithelial cells. Lubricin messenger RNA is also present in lacrimal and meibomian glands, as well as in a number of other tissues. Absence of lubricin in PRG4 knockout mice is associated with a significant increase in corneal fluorescein staining. Our studies also show that lubricin functions as an effective friction-lowering boundary lubricant at the human cornea-eyelid interface. This effect is specific and cannot be duplicated by the use of hyaluronate or bovine serum albumin solutions.

CONCLUSIONS AND RELEVANCE

Our results show that lubricin is transcribed, translated, and expressed by ocular surface epithelia. Moreover, our findings demonstrate that lubricin presence significantly reduces friction between the cornea and conjunctiva and that lubricin deficiency may play a role in promoting corneal damage.

摘要

重要性

黏蛋白可能是干眼病和隐形眼镜佩戴中发生的角膜和结膜上皮病的重要屏障。

目的

检验以下假设,即作为边界润滑剂的黏蛋白(即蛋白聚糖 4 [PRG4])由眼表面上皮产生,并起到保护角膜和结膜的作用,使其免受眼睑眨眼产生的显著剪切力的影响,以及黏蛋白缺乏会增加眼表面的剪切应力并促进角膜损伤。

设计、设置和参与者:对人、猪和鼠组织和细胞进行了分子生物学、免疫组织化学和摩擦学研究,并用野生型和 PRG4 敲除小鼠评估了角膜损伤。

结果

我们的研究结果表明,黏蛋白由角膜和结膜上皮细胞转录和翻译。泪腺和睑板腺以及许多其他组织中也存在黏蛋白信使 RNA。PRG4 敲除小鼠中黏蛋白的缺失与角膜荧光素染色显著增加有关。我们的研究还表明,黏蛋白在人眼角膜-眼睑界面作为一种有效的降低摩擦的边界润滑剂发挥作用。这种作用是特异性的,无法通过使用透明质酸钠或牛血清白蛋白溶液来复制。

结论和相关性

我们的研究结果表明,黏蛋白由眼表面上皮细胞转录、翻译和表达。此外,我们的研究结果表明,黏蛋白的存在显著降低了角膜和结膜之间的摩擦,并且黏蛋白缺乏可能在促进角膜损伤中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/def4/3887468/571f38533e87/nihms536281f1.jpg

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