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Kinetics of Apoptotic Cells in Experimental Autoimmune Uveoretinitis

¹ From the Department of Ophthalmology, Kurume University School of Medicine, Kurume, Japan; the ² Department of Ophthalmology, Tokyo Medical and Dental University School of Medicine, Japan; and the ³ Department of Pathology, Kurume University School of Medicine, Kurume, Japan.

PURPOSE. To investigate the role of apoptosis in immunopathogenic mechanisms of experimental autoimmune uveoretinitis (EAU), the kinetics of apoptotic cells and expression of Fas and Fas ligand (FasL) in the eye with EAU were studied.

METHODS. Male inbred Lewis rats were immunized with S-antigen (40 µg/rat), and eyes were examined to detect apoptotic cells on days 1, 4, 8, and 10 post-immunization and days 0, 2, 4, 6, and 8 after the onset of EAU. The clinical and pathologic scores were used for estimating EAU. Apoptotic cells were analyzed by TdT-mediated dUTP nick-end labeling, electron microscopic and immunohistologic examinations, and agarose gel electrophoresis. The anti–rat Fas and anti–rat FasL antibodies were used to examine the expression of Fas and FasL.

RESULTS. Apoptotic cells were detected in the infiltrating cells in the aqueous humor, the vitreous body, the iris-ciliary body, and the retina. Apoptotic cells were observed as early as the day of EAU onset and reached a peak on day 2 after the disease onset. Fas and FasL were expressed on the infiltrating cells in the aqueous humor and the vitreous. FasL was expressed on resident cells of the ciliary body. The kinetics of the expression of FasL corresponded with the kinetics of apoptotic cells.

CONCLUSIONS. Fas–FasL–mediated apoptosis is considered to occur in the eye with EAU and plays a role in the immunopathogenic mechanisms to eliminate ocular infiltrating cells, thereby downregulating the inflammatory processes.

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