Koga M, Hiromatsu Y, Jimi A, Inoue Y, Nonaka K
Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan.
Thyroid. 1998 Apr;8(4):311-8. doi: 10.1089/thy.1998.8.311.
In order to investigate the possible involvement of apoptosis in the pathogenesis of thyroid-associated ophthalmopathy (TAO), we studied the expression of Fas, Fas ligand (FasL), and Bcl-2 in extraocular muscle tissues from patients with TAO by immunohistochemistry using monoclonal antibodies against Fas, FasL, and Bcl-2. Apoptosis was detected by in situ end-labeling of fragmented DNA. Apoptosis was detected in extraocular muscle tissues from 17 of 19 patients with TAO and, to a smaller degree in 4 of 7 normal control subjects. The mean percentages of apoptotic nuclei were 12.1% in TAO eye muscle fibers and 16.4% in TAO interstitial cells, compared with 2.2% and 0.4% in normal eye muscle fibers and interstitial cells, respectively. The percentage of apoptotic nuclei in eye muscle fibers correlated with the enlargement of eye muscle tissue (r = 0.47, p < 0.05). Fas was demonstrated on the surfaces of extraocular muscle fibers in 11 of 18 patients with TAO, but not in normal extraocular muscle tissues. Neither TAO nor normal extraocular muscle tissues expressed Bcl-2. FasL was detected in infiltrating mononuclear cells in extraocular muscle tissue from a patient with TAO. These data suggest that Fas-mediated apoptosis may occur in extraocular muscle tissue from patients with TAO and may be involved in the late stage of TAO.
为了研究细胞凋亡在甲状腺相关眼病（TAO）发病机制中的可能作用，我们采用抗Fas、Fas配体（FasL）和Bcl-2的单克隆抗体，通过免疫组织化学方法研究了TAO患者眼外肌组织中Fas、FasL和Bcl-2的表达。通过对断裂DNA进行原位末端标记检测细胞凋亡。在19例TAO患者中的17例眼外肌组织中检测到细胞凋亡，在7例正常对照者中的4例也有较小程度的细胞凋亡。TAO眼肌纤维中凋亡细胞核的平均百分比为12.1%，TAO间质细胞中为16.4%，而正常眼肌纤维和间质细胞中分别为2.2%和0.4%。眼肌纤维中凋亡细胞核的百分比与眼肌组织肿大相关（r = 0.47，p < 0.05）。18例TAO患者中有11例眼外肌纤维表面显示有Fas，而正常眼外肌组织中未显示。TAO和正常眼外肌组织均不表达Bcl-2。在1例TAO患者的眼外肌组织浸润单核细胞中检测到FasL。这些数据表明，Fas介导的细胞凋亡可能发生在TAO患者的眼外肌组织中，并可能参与TAO的晚期阶段。
