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

Keratocyte apoptosis: implications on corneal wound healing, tissue organization, and disease.
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发表时间:
1998-02
影响因子:
4.4
通讯作者:
S. Wilson;W. J. Kim
S. Wilson;W. J. Kim
中科院分区:
医学2区
文献类型:
--
作者:
S. Wilson;W. J. Kim

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有时候,一个简单的发现改变了我们对一个系统的生物学的基本认识,而这个发现却打开了一扇通往广阔新视野的大门。观察到角膜上皮损伤后,前角化细胞消失,随后发现这种消失是通过细胞程序性死亡或凋亡发生的。最近的研究错误地认为Nakayasu和Crosson最初观察到角膜上皮刮伤后前角化细胞消失。通常情况下,最初的发现早得多了。Dohlman等人在30年前报道上皮刮伤后上皮下的角化细胞消失。这些早期研究的作者假设角化细胞的消失可归因于机械损伤、暴露于大气或渗透变化。这些关键观察的根本重要性没有得到重视,可能是因为我们对生物系统中细胞凋亡的重要性的理解和检测这种特殊形式的细胞死亡的工具还没有发展到发现的种子落在肥沃土壤上的程度。在这些最初的角膜研究和其他组织中凋亡的早期观察之间的冷漠受体的平行是惊人的。然而,幸运的是,Campos等人再次观察到角膜角质细胞消失的现象,并将其扩展到灵长类动物。此后不久,Wilson等人证明角膜上皮损伤后角质细胞的消失是由细胞凋亡介导的。在视觉研究中,一些临床医生和科学家对于使用细胞凋亡这个术语来描述上皮损伤后角质细胞的死亡一直犹豫不决。通常,这种怀疑是基于这样一种观点,即细胞凋亡或程序性细胞死亡应该保留给与多细胞生物发育相关的基因调控的细胞死亡。然而,细胞凋亡在功能上被定义为生物体在不释放降解酶和其他可能损害周围组织和细胞的细胞成分的情况下,用来清除不需要的细胞的一种不受控制的细胞死亡形式。因此,细胞凋亡与许多器官的发育、体内平衡、感染、伤口愈合和疾病的病理生理有关。也许
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