Keratocyte apoptosis: implications on corneal wound healing, tissue organization, and disease.

Occasionally our fundamental perceptions regarding the biology of a system are altered by a simple finding that has the effect of prying open a door to a broad new horizon. Such is the case with the observation that the anterior keratocytes disappear after the wounding of the corneal epithelium and the subsequent discovery that this disappearance occurs through programmed cell death or apoptosis. Recent studies erroneously credited Nakayasu and Crosson with the initial observation that anterior keratocytes disappear after a scrape injury to the corneal epithelium. As is frequently the case, the original finding had been made much earlier. Dohlman et al. reported 30 years ago that the keratocytes underlying the epithelium disappeared after an epithelial scrape injury. The authors of these early studies' hypothesized that the disappearance of keratocytes was attributable to mechanical injury, exposure to the atmosphere, or osmotic changes. The fundamental importance of these key observations was not appreciated, probably because our understanding of the significance of apoptosis in biologic systems and the tools to detect this special form of cell death had not developed to the point that the seeds of discovery fell on fertile soil. The parallel between the apathetic receptions given these initial corneal studies and the early observations on apoptosis in other tissues is striking. Fortunately, however, the corneal phenomenon of keratocyte disappearance was observed once again and was extended to the primates by Campos et al. Shortly thereafter Wilson et al. demonstrated that the disappearance of keratocytes in response to corneal epithelial wounding was mediated by apoptosis. There has been hesitancy on the part of some clinicians and scientists in vision research to use the term apoptosis to describe the death of keratocytes after epithelial injury. Usually, this skepticism is based on the view that the term apoptosis or programmed cell death should be reserved for a genetically regulated cell death that is associated with the development of a multicellular organism. However, apoptosis is defined functionally as an involutional and controlled form of cell death used by an organism to rid itself of unwanted cells without the release of degradative enzymes and other cellular components that would damage surrounding tissue and cells. As such, apoptosis has been associated with the development, homeostasis, infection, wound healing, and pathophysiology of disease in many organs.' Perhaps