BACKGROUND Tauopathy in the central nervous system (CNS) is a histopathological hallmark of frontotemporal dementia (FTD) and Alzheimer's disease (AD). Although AD is accompanied by various ocular changes, the effects of tauopathy on the integrity of the cornea, which is densely innervated by the peripheral nervous system and is populated by resident dendritic cells, is still unknown. The aim of this study was to investigate if neuroimmune interactions in the cornea are affected by CNS tauopathy. METHODS Corneas from wild type (WT) and transgenic rTg4510 mice that express the P301L tau mutation were examined at 2, 6, 8, and 11 months. Clinical assessment of the anterior segment of the eye was performed using spectral domain optical coherence tomography. The density of the corneal epithelial sensory nerves and the number and field area of resident epithelial dendritic cells were assessed using immunofluorescence. The immunological activation state of corneal and splenic dendritic cells was examined using flow cytometry and compared between the two genotypes at 9 months of age. RESULTS Compared to age-matched WT mice, rTg4510 mice had a significantly lower density of corneal nerve axons at both 8 and 11 months of age. Corneal nerves in rTg4510 mice also displayed a higher percentage of beaded nerve axons and a lower density of epithelial dendritic cells compared to WT mice. From 6 months of age, the size of the corneal dendritic cells was significantly smaller in rTg4510 compared to WT mice. Phenotypic characterization by flow cytometry demonstrated an activated state of dendritic cells (CD86+ and CD45+ CD11b+CD11c+) in the corneas of rTg4510 compared to WT mice, with no distinct changes in the spleen monocytes/dendritic cells. At 2 months of age, there were no significant differences in the neural or immune structures between the two genotypes. CONCLUSIONS Corneal sensory nerves and epithelial dendritic cells were altered in the rTg4510 mouse model of tauopathy, with temporal changes observed with aging. The activation of corneal dendritic cells prior to the gradual loss of neighboring sensory nerves suggests an early involvement of corneal immune cells in tau-associated pathology originating in the CNS.

中文翻译：

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中枢神经系统tauopathy小鼠角膜神经免疫表型的新变化。

背景技术中枢神经系统（CNS）中的tauopathy是额颞叶痴呆（FTD）和阿尔茨海默氏病（AD）的组织病理学标志。尽管AD伴随着各种眼部变化，但是tauopathy对角膜完整性的影响仍然未知，该角膜的完整性由周围神经系统神经支配并由驻留的树突状细胞组成。这项研究的目的是调查中枢神经系统tauopathy是否会影响角膜中的神经免疫相互作用。方法在第2、6、8和11个月时检查来自野生型（WT）和表达P301L tau突变的转基因rTg4510小鼠的角膜。使用光谱域光学相干断层扫描对眼睛的前段进行临床评估。使用免疫荧光评估角膜上皮感觉神经的密度以及驻留上皮树突状细胞的数量和视野面积。使用流式细胞仪检查角膜和脾树突状细胞的免疫激活状态，并在9个月大时比较这两种基因型。结果与年龄匹配的WT小鼠相比，rTg4510小鼠在8个月和11个月大时，其角膜神经轴突的密度均显着降低。与WT小鼠相比，rTg4510小鼠的角膜神经还显示出更高比例的串珠状神经轴突和较低密度的上皮树突状细胞。从6个月大起，与野生型小鼠相比，rTg4510中的角膜树突状细胞的大小显着减小。与野生型小鼠相比，流式细胞术的表型特征表明rTg4510角膜中树突状细胞（CD86 +和CD45 + CD11b + CD11c +）的活化状态，而脾单核细胞/树突状细胞没有明显变化。在两个月大的时候，两种基因型之间在神经或免疫结构上没有显着差异。结论在rTg4510 tauopathy小鼠模型中，角膜感觉神经和上皮树突状细胞发生了改变，随着年龄的增长观察到时间变化。在逐渐丧失邻近的感觉神经之前，角膜树突状细胞的活化表明角膜免疫细胞早日参与了起源于中枢神经系统的tau相关病理。脾单核细胞/树突状细胞无明显变化。在两个月大的时候，两种基因型之间在神经或免疫结构上没有显着差异。结论在rTg4510 tauopathy小鼠模型中，角膜感觉神经和上皮树突状细胞发生了改变，随着年龄的增长观察到时间变化。在逐渐丧失邻近的感觉神经之前，角膜树突状细胞的活化表明角膜免疫细胞早日参与了起源于中枢神经系统的tau相关病理。脾单核细胞/树突状细胞无明显变化。在两个月大的时候，两种基因型之间在神经或免疫结构上没有显着差异。结论在rTg4510 tauopathy小鼠模型中，角膜感觉神经和上皮树突状细胞发生了改变，随着年龄的增长观察到时间变化。在逐渐丧失邻近的感觉神经之前，角膜树突状细胞的活化表明角膜免疫细胞早日参与了起源于中枢神经系统的tau相关病理。