Interaction of invasive bacteria with host signaling pathways

PURPOSE: Programmed cell death (apoptosis) is the controlled death of cells that occurs with minimal collateral damage to surrounding cells or tissue during development, homeostasis, and wound healing. The authors hypothesize the keratocyte apoptosis is an initiating factor in the wound-healing response after refractive surgical procedures. To evaluate the effects of different corneal manipulations, keratocyte apoptosis was examined qualitatively and quantitatively after traditional epithelial scrape-photorefractive keratectomy (PRK), transepithelial PRK, removal of a cap of superficial cornea using a microkeratome, production of a flap of superficial cornea with a microkeratome, and laser-assisted in situ keratomileusis (LASIK) compared with unwounded controls in rabbit corneas. METHODS: Refractive surgical procedures or their components were performed in rabbit eyes. Keratocyte apoptosis was monitored using the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling assay to detect DNA fragmentation. Cellular morphologic changes were evaluated by electron microscope examination. RESULTS: Keratocyte apoptosis was noted with each refractive procedure or corneal manipulation and was variable from eye to eye with each procedure. Transepithelial PRK was associated with the lowest levels of central corneal apoptosis, even if the stromal surface was scraped after the procedure. Keratocyte apoptosis is confined to the superficial stroma extending to a depth of approximately 50 microns to 75 microns after epithelial scrape-PRK and transepithelial PRK. Apoptosis was noted in the deeper central corneal keratocytes located anteriorly and posteriorly to the lamellar cut in LASIK. CONCLUSIONS: There are qualitative and quantitative differences in keratocyte apoptosis between LASIK, epithelial scrape-PRK, and transepithelial PRK. Epithelial injury is an important factor modulating keratocyte apoptosis. The level and distribution of keratocyte apoptosis, along with subsequent repopulation by activated stromal keratocytes, are likely to be important determinants of corneal wound healing associated with variability and regression after PRK and LASIK. Transepithelial PRK induces low levels of keratocyte apoptosis, and, therefore, this approach may be useful for treating higher levels of myopia and for retreatment after regression.