Cornea and Ocular Surface Disease Unit, Eye Repair Lab, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Lymphocyte Activation Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Exp Eye Res. 2022 Jul;220:109128. doi: 10.1016/j.exer.2022.109128. Epub 2022 May 27.
The aim of this work was to assess corneal endothelial morphology in a well-established acute graft-versus-host disease (GVHD) murine model and to quantify the expression of neurokinin-1 receptor (NK1R) in the corneal endothelium during ocular GVHD (oGVHD). Pre-conditioning was performed in BALB/c using myeloablative total body irradiation. Subsequently, allogeneic bone marrow transplantation was performed without (BM) or with mature T cells (BM + T). Corneal transparency was monitored with in vivo biomicroscopy. After sacrifice, corneal thickness and endothelial cell number were measured, and the expression of NK1R was investigated in the corneal endothelium through immunofluorescence and quantified by immunohistochemistry. Mice presenting oGVHD showed a significant reduction in endothelial cell number compared to control animals (p < 0.0001). NK1R expression was significantly increased in oGVHD mice endothelium (p < 0.05). Corneal transparency and thickness were unchanged in all groups. Our results suggest that oGVHD affects the corneal endothelium, inducing a reduction of the cell number, and that this is associated with increased expression of the pro-inflammatory marker NK1R.
本研究旨在评估一种成熟的急性移植物抗宿主病（GVHD）小鼠模型中的角膜内皮形态，并在眼 GVHD（oGVHD）期间定量分析角膜内皮中神经激肽-1 受体（NK1R）的表达。在 BALB/c 小鼠中进行预处理，采用全身照射进行骨髓清除。随后，进行异基因骨髓移植，不（BM）或用成熟 T 细胞（BM+T）。通过活体生物显微镜监测角膜透明度。处死动物后，测量角膜厚度和内皮细胞数量，并通过免疫荧光法检测角膜内皮中 NK1R 的表达，并通过免疫组织化学法进行定量分析。与对照组动物相比，出现 oGVHD 的小鼠的内皮细胞数量显著减少（p<0.0001）。oGVHD 小鼠内皮细胞中 NK1R 的表达显著增加（p<0.05）。所有组的角膜透明度和厚度均无变化。我们的结果表明，oGVHD 影响角膜内皮，导致细胞数量减少，并且这与促炎标志物 NK1R 的表达增加有关。
