Koudouna Elena, Okumura Naoki, Okazaki Yugo, Nakano Shinichiro, Inoue Ryota, Fullwood Nigel J, Hori Junko, Kinoshita Shigeru, Koizumi Noriko
Department of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.
Department of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan 2Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Invest Ophthalmol Vis Sci. 2017 Jan 1;58(1):242-251. doi: 10.1167/iovs.16-20019.
Corneal endothelial cell density undergoes a progressive decrease for many years after transplantation, eventually threatening patients with late endothelial failure. The purpose of this study was to investigate the possibility of an immunologic response in successfully grafted corneal endothelium.
The corneal endothelium of patients who had undergone corneal transplantation was evaluated by specular microscopy. Rabbit models were subjected to penetrating keratoplasty (PK) with either syngeneic or allogeneic corneal transplants and Descemet's stripping endothelial keratoplasty (DSEK) with allogeneic corneal transplants. The presence of immune cells and expression of proinflammatory cytokines were determined by immunostaining. The corneal endothelium and immune cells were also evaluated by scanning electron microscopy.
Scanning slit contact specular microscopy of patients with no features of graft rejection revealed cell-like white dots on the grafted corneal endothelium. The corneal endothelium of the allogeneic PK and DSEK rabbit models displayed the presence of immune cells, including CD4+ T-helper cells, CD8+ cytotoxic T cells, CD20+ B lymphocytes, CD68+ macrophages, and neutrophils, but these immune cells were rarely observed in the syngeneic PK model. These immune cells also produced proinflammatory cytokines. Notably, some of the corneal endothelial cells situated near these immune cells exhibited features of apoptosis.
T lymphocytes, B lymphocytes, macrophages, and neutrophils are present on the grafted corneal endothelium in both PK and DSEK allogeneic rabbit models. The potential involvement of immune cells as an underlying pathophysiology for late endothelial failure deserves further examination.
角膜移植术后多年角膜内皮细胞密度会逐渐下降,最终使患者面临晚期内皮功能衰竭的风险。本研究旨在探讨成功移植的角膜内皮发生免疫反应的可能性。
通过镜面显微镜对接受角膜移植患者的角膜内皮进行评估。兔模型分别接受同基因或异基因角膜移植的穿透性角膜移植术(PK)以及异基因角膜移植的Descemet膜剥脱内皮角膜移植术(DSEK)。通过免疫染色确定免疫细胞的存在和促炎细胞因子的表达。还通过扫描电子显微镜对角膜内皮和免疫细胞进行评估。
对无移植排斥特征患者的扫描裂隙接触镜面显微镜检查显示,移植的角膜内皮上有细胞样白点。异基因PK和DSEK兔模型的角膜内皮显示存在免疫细胞,包括CD4 +辅助性T细胞、CD8 +细胞毒性T细胞、CD20 + B淋巴细胞、CD68 +巨噬细胞和中性粒细胞,但在同基因PK模型中很少观察到这些免疫细胞。这些免疫细胞也产生促炎细胞因子。值得注意的是,位于这些免疫细胞附近的一些角膜内皮细胞表现出凋亡特征。
在PK和DSEK异基因兔模型中,移植的角膜内皮上均存在T淋巴细胞、B淋巴细胞、巨噬细胞和中性粒细胞。免疫细胞作为晚期内皮功能衰竭潜在的病理生理学机制值得进一步研究。