Lacrimal Gland Innervation Is Not Altered with the Onset and Progression of Disease in a Murine Model of Sjögren's Syndrome

Driss Zoukhri , Robin R. Hodges, Darlene A. Dartt
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引用次数: 34

Abstract

The lacrimal glands of patients with Sjögren's syndrome develop extensive lymphocytic infiltration, but also contain a large number of seemingly healthy looking acinar and ductal cells. Despite this, the secretory function of this tissue is impaired, leading to aqueous tear-deficient dry eye. This raises the possibility that there is a defect in the neural innervation of the remaining portion of the lacrimal gland. To test for this possibility, we used antibodies specific to various markers of the parasympathetic, sympathetic, and sensory nerves and performed immunohistochemical analyses of lacrimal glands from a murine model of Sjögren's syndrome, the MRL/Mp-Fas-lpr/lpr(MRL/lpr) and the control mice MRL/Mp−+/+ (MRL/+). Our results show that the MRL/lpr, but not the MRL/+, lacrimal glands become infiltrated with lymphocytes starting at 8 weeks of age which worsens by 12 and 18 weeks. The density and the pattern of parasympathetic, sympathetic, and sensory innervation of the noninflamed acinar tissue of MRL/lpr lacrimal glands, at 4, 8, 12, and 18 weeks, is indistinguishable from that of age-matched control MRL/+ lacrimal glands. We conclude that the loss of the secretory function in Sjögren's syndrome lacrimal glands is not due to a loss or decrease of its innervation.

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在小鼠Sjögren综合征模型中,泪腺神经支配不随疾病的发生和进展而改变
Sjögren综合征患者的泪腺出现广泛的淋巴细胞浸润,但也含有大量看似健康的腺泡和导管细胞。尽管如此,该组织的分泌功能受损,导致水性泪液缺乏性干眼症。这就提出了泪腺剩余部分的神经支配存在缺陷的可能性。为了验证这种可能性,我们使用了针对副交感神经、交感神经和感觉神经的各种标记物的抗体,并对Sjögren综合征小鼠模型、MRL/Mp- fas -lpr/lpr(MRL/lpr)和对照小鼠MRL/Mp−+/+ (MRL/+)的泪腺进行了免疫组织化学分析。我们的研究结果表明,MRL/lpr,而不是MRL/+,泪腺在8周龄开始浸润淋巴细胞,并在12和18周龄时恶化。在4、8、12和18周时,MRL/lpr泪腺非炎症腺泡组织的副交感神经、交感神经和感觉神经的密度和模式与年龄匹配的对照MRL/lpr泪腺没有区别。我们得出结论,在Sjögren综合征泪腺分泌功能的丧失不是由于其神经支配的损失或减少。
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