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奥沙利铂诱导的和糖尿病诱导的多发性神经病之间,眼表变化存在显著差异。

Ocular Surface Changes Differ Significantly Between Oxaliplatin- and Diabetes-Induced Polyneuropathy.

作者信息

Schicht Martin, Sisignano Marco, Farger Jessica, Wedel Saskia, Phunchago Nichapa, Perumal Natarajan, Manicam Caroline, Scholich Klaus, Geisslinger Gerd, Paulsen Friedrich, Lütjen-Drecoll Elke

机构信息

Institute of Functional and Clinical Anatomy, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany.

Institute of Clinical Pharmacology, Goethe University, 60590 Frankfurt am Main, Germany.

出版信息

Int J Mol Sci. 2025 Feb 22;26(5):1884. doi: 10.3390/ijms26051884.

Abstract

Dry eye disease (DED) is often seen in patients with polyneuropathies (PNs), but the relationship between the different forms of PNs and DED is not known. In oxaliplatin (Ox-)-treated mice with PNs, morphological changes in the sciatic nerve (SN), dorsal root ganglia (DRG), trigeminal ganglia (TG), and the ocular tissues involved in tear formation were investigated. In addition, the tear proteomics and the gene expression of related proteins in the ocular surface tissues as well as inflammatory factors were analyzed. There were significant changes in six tear proteins compared to the controls, with respective changes in gene expression in the ocular tissues. Morphologically, there was a decrease in the number of conjunctival goblet cells and changes in the myofibroblasts surrounding the Meibomian glands. The lacrimal gland appeared normal. In the SN, there was a slight decrease in the number of mitochondria without signs of inflammation. In the DRG, 30-50% of the small- and medium-sized neuronal cells had swollen mitochondria. In contrast, the mitochondria of the TG were unremarkable. The changes in the tear film proteins and the ocular tissue morphology involved in tear formation in OPN differed significantly from those previously described in DPN mice, despite a similar mechanical hypersensitivity and similar morphological features of the DRG. In DPN, these changes led to aqueous-deficient dry eye disease, whereas in OPN, they resulted in evaporative DED. Furthermore, in contrast to DPN, the TG in OPN showed no morphological alterations, which indicates differences in the peripheral nerve changes and ocular nerve damage between the two conditions.

摘要

干眼症(DED)在患有多发性神经病(PNs)的患者中很常见,但不同形式的PNs与DED之间的关系尚不清楚。在接受奥沙利铂(Ox-)治疗的PNs小鼠中,研究了坐骨神经(SN)、背根神经节(DRG)、三叉神经节(TG)以及参与泪液形成的眼组织的形态学变化。此外,还分析了泪液蛋白质组学、眼表组织中相关蛋白质的基因表达以及炎症因子。与对照组相比,六种泪液蛋白质有显著变化,眼组织中的基因表达也有相应变化。形态学上,结膜杯状细胞数量减少,睑板腺周围的肌成纤维细胞发生变化。泪腺外观正常。在SN中,线粒体数量略有减少,无炎症迹象。在DRG中,30%-50%的中小型神经元细胞线粒体肿胀。相比之下,TG的线粒体无明显变化。尽管OPN小鼠与DPN小鼠有相似的机械性超敏反应和相似的DRG形态特征,但OPN中参与泪液形成的泪膜蛋白和眼组织形态变化与先前在DPN小鼠中描述的有显著差异。在DPN中,这些变化导致水液缺乏型干眼症,而在OPN中,它们导致蒸发型DED。此外,与DPN不同,OPN中的TG没有形态学改变,这表明两种情况下周围神经变化和眼神经损伤存在差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c6b/11900114/180a74a14580/ijms-26-01884-g001.jpg

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