POSSIBLE INVOLVEMENT OF FAS-MEDIATED APOPTOSIS IN EYE MUSCLE-TISSUE FROM PATIENTS WITH THYROID-ASSOCIATED OPHTHALMOPATHY

In order to investigate the possible involvement of apoptosis in the p athogenesis 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 monoclon al antibodies against Pas, FasL, and Bcl-2. Apoptosis was detected by in situ end-labeling of fragmented DNA. Apoptosis was detected in extr aocular muscle tissues from 17 of 19 patients with TAO and, to a small er degree in 4 of 7 normal control subjects. The mean percentages of a poptotic nuclei were 12.1% in TAO eye muscle fibers and 16.4% in TAO i nterstitial cells, compared with 2.2% and 0.4% in normal eye muscle fi bers and interstitial cells, respectively. The percentage of apoptotic nuclei in eye muscle fibers correlated with the enlargement of eye mu scle 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 i n normal extraocular muscle tissues. Neither TAO nor normal extraocula r muscle tissues expressed Bcl-2. Fast was detected in infiltrating mo nonuclear cells in extraocular muscle tissue from a patient with TAO. These data suggest that Fas-mediated apoptosis may occur in extraocula r muscle tissue from patients with TAO and may be involved in the late stage of TAO.