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人眼淚腺中的 GPR-68。檢測及其在乾眼症發病機理中的可能作用。

GPR-68 in human lacrimal gland. Detection and possible role in the pathogenesis of dry eye disease.

机构信息

Department of Clinical Neuroscience, Lab DOHF, Karolinska Institutet, Stockholm, Sweden.

出版信息

J Fr Ophtalmol. 2022 Oct;45(8):921-927. doi: 10.1016/j.jfo.2022.02.009. Epub 2022 May 24.

DOI:10.1016/j.jfo.2022.02.009
PMID:35623913
Abstract

INTRODUCTION

In parallel to ocular surface disease in dry eye there is often a dysfunctionality of the lacrimal gland apparatus. The functionality of the lacrimal gland is of major importance for maintenance of ocular surface integrity and health, even in conditions of enhanced stimulation and secretion requirements. Such enhanced secretion demands can push the lacrimal gland to its limits, with maximized tear fluid secretion and increased flow through the lacrimal ducts. The goal of this study was to investigate whether G protein-coupled receptor GPR-68 is present in the lacrimal gland, as this protein has recently been shown to be sensitive to flow rate and osmolarity.

METHODS

For this purpose, de-identified sections of human lacrimal gland tissue were stained for the presence of G protein-coupled receptor 68 with specific antibodies using immunohistochemistry.

RESULTS

Specific staining was detected in the acini and ducts of human lacrimal gland. In the ducts, the specific staining was found around the lumen of the ducts. In the acini, the specific staining was observed more towards the lumen but also intercellularly between the acinar cells.

DISCUSSION

The detection of G protein-coupled receptor GPR-68 in the lacrimal gland, especially around the lumen of the ducts, raises the question about its function and purpose. Activation of GPR68 leads to modification of various cell functions and is associated with regulation of inflammation. Accordingly, enhanced, secretion-induced, augmentation of flow might exert fluid flow stress on the ducts and acini. This might lead to transient, localized activation of GPR-68 and secondary inflammation within the gland. Depending on the intensity, continuity or repetitive nature of the stimuli, exhaustion of the lacrimal gland secretion capacity might follow, and chronicity of the inflammation in the parenchyma as well as around the ducts might be a consequence.

CONCLUSION

G protein-coupled receptor GPR-68, sensitive to flow, is present in the human lacrimal gland. Increased flow, triggered by sensations such as are typical for dry eye, might lead to local inflammation. It is possible that these sensations might serve as a better indicator for the need and success of therapy than the clinical signs of dry eye disease, at least in the early stages of the disease.

摘要

简介

在干眼症的眼表疾病的同时,常常存在泪腺装置的功能障碍。泪腺的功能对于维持眼表完整性和健康至关重要,即使在刺激和分泌需求增强的情况下也是如此。这种增强的分泌需求可以使泪腺达到极限,最大程度地分泌泪液并增加泪液通过泪道的流量。本研究的目的是研究 G 蛋白偶联受体 GPR-68 是否存在于泪腺中,因为最近已经证明该蛋白对流速和渗透压敏感。

方法

为此,使用免疫组织化学方法,用人泪腺组织的去鉴定切片,用特异性抗体检测 G 蛋白偶联受体 68 的存在。

结果

在人泪腺的腺泡和导管中检测到特异性染色。在导管中,特异性染色发现于导管的腔周围。在腺泡中,特异性染色观察到更靠近腔,但也在腺泡细胞之间的细胞间。

讨论

G 蛋白偶联受体 GPR-68 在泪腺中的检测,特别是在导管的腔周围,提出了其功能和目的的问题。GPR68 的激活导致各种细胞功能的改变,并与炎症的调节有关。因此,增强的、分泌诱导的、增加的流量可能对导管和腺泡施加流体流动应力。这可能导致 GPR-68 的瞬时、局部激活和腺体内的继发性炎症。根据刺激的强度、连续性或重复性,可能会耗尽泪腺的分泌能力,并且可能会导致实质和导管周围的炎症慢性化。

结论

对流量敏感的 G 蛋白偶联受体 GPR-68 存在于人泪腺中。由干眼症等感觉引起的流量增加可能导致局部炎症。这些感觉可能比干眼症疾病的临床迹象更能作为治疗需求和成功的更好指标,至少在疾病的早期阶段是如此。

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