Purpose

Diabetes mellitus (DM) is a leading risk factor for corneal neuropathy and dry eye disease (DED). Another common consequence of DM is diabetic peripheral polyneuropathy (DPN). Both complications affect around 50 % of the DM patients but the relationship between DM, DED and DPN remains unclear.

Methods

In this study, we examined mice with early onset of DM and PN after streptozotocin (STZ)-induced diabetes (DPN). We compared the early morphological changes of the sciatic nerve, dorsal root and trigeminal ganglia with the changes in the ocular surface, including tear proteomic and we also investigated respective changes in the gene expressions and morphological alterations in the eye tissues involved in tear production.

Results

The lacrimal gland, conjunctival goblet cells and cornea showed morphological changes along with alterations in tear proteins without any obvious signs of ocular surface inflammation. The gene expression for respectively altered tear proteins i.e., of Clusterin in cornea, Car6, Adh3a1, and Eef1a1 in eyelids, and Pigr in the lacrimal gland also showed significant changes compared to control mice. In the trigeminal ganglia like in the dorsal root ganglia neuronal cells showed swollen mitochondria and, in the latter, there was a significant increase of NADPH oxidases and MMP9 suggestive of oxidative and neuronal stress. In the dorsal root ganglia and the sciatic nerve, there was an upregulation of a number of pro-inflammatory cytokines and pain-mediating chemokines.

Conclusion

The early ocular changes in DM Mice only affect the lacrimal gland. Which, is reflected in the tear film composition of DPN mice. Due to the high protein concentration in tear fluid in humans, proteomic analysis in addition to noninvasive investigation of goblet cells and cornea can serve as a tools for the early diagnosis of DPN, DED in clinical practice. Early treatment could delay or even prevent the ocular complications of DM such as DED and PN.

中文翻译：

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链脲佐菌素诱导的糖尿病和糖尿病性多发性神经病小鼠的眼表变化

目的

糖尿病（DM）是角膜神经病变和干眼病（DED）的主要危险因素。DM 的另一个常见后果是糖尿病周围性多发性神经病 (DPN)。这两种并发症影响约 50% 的 DM 患者，但 DM、DED 和 DPN 之间的关系仍不清楚。

方法

在这项研究中，我们检查了链脲佐菌素 (STZ) 诱导的糖尿病 (DPN) 后早期出现 DM 和 PN 的小鼠。我们将坐骨神经、背根和三叉神经节的早期形态变化与眼表的变化（包括泪液蛋白质组）进行了比较，并且我们还研究了与泪液产生有关的眼组织的基因表达和形态变化的各自变化。

结果

泪腺、结膜杯状细胞和角膜表现出形态变化以及泪液蛋白的变化，但没有任何明显的眼表炎症迹象。与对照小鼠相比，分别改变的泪液蛋白（即角膜中的 Clusterin、眼睑中的 Car6、Adh3a1 和 Eef1a1 以及泪腺中的Pigr ）的基因表达也显示出显着变化。在三叉神经节中，就像在背根神经节中一样，神经元细胞显示出线粒体肿胀，并且在后者中，NADPH 氧化酶和 MMP9 显着增加，表明存在氧化和神经元应激。在背根神经节和坐骨神经中，许多促炎细胞因子和疼痛介导的趋化因子上调。

结论

DM 小鼠的早期眼部变化仅影响泪腺。其中，反映在 DPN 小鼠的泪膜成分上。由于人类泪液中的蛋白质浓度较高，除了杯状细胞和角膜的无创研究之外，蛋白质组分析可以作为临床实践中早期诊断 DPN、DED 的工具。早期治疗可以延缓甚至预防 DM 的眼部并发症，如 DED 和 PN。