Apoptosis in human non-necrotizing stromal herpes simplex keratitis

Background: Herpes simplex virus (HSV-1) stromal keratitis is an immune-med iated disease. Recently, it has been shown that infection of cells with HSV -1 induces apoptosis. In this study we investigated the presence of apoptot ic cell death in keratectomy specimens from patients with HSV-1 stromal ker atitis. Patients and Methods: Keratectomy specimens from six patients with HSV-1 no n-necrotizing stromal keratitis were chosen and compared to healthy corneas . Paraffin sections were analyzed histologically and cryosections were stud ied by the immunoperoxidase technique for the presence of HSV-1, Fas and Fa sLigand (FasL) antigens. Apoptosis was assessed by TUNEL assay (TdT-mediate d dUTP nick-end labeling). Results: In healthy corneas, Fas was detected in the epithelium, keratocyte s and endothelium; FasL was present in the epithelium and endothelium; TUNE L-positive cells were only found in the superficial epithelial cells. In co ntrast, inflammatory cells and scars were found in all HSV-diseased corneas ; HSV-1 antigen was detected in only one specimen. Cells within inflammator y infiltrations and epithelium were apoptotic. Fas was detected in all corn eal cell layers and inflammatory cells. FasL was restricted to areas of inf lammation. Conclusions: The data suggest that apoptosis plays a role in the pathogenes is of HSV keratitis. The Fas-FasL system appears to be involved in the indu ction of apoptosis. Apoptosis could be involved in the depletion of inflamm atory cells in the cornea and may limit the extension of viral replication to the eye.