Nickells R W
Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison 53792, USA.
Surv Ophthalmol. 1999 Jun;43 Suppl 1:S151-61. doi: 10.1016/s0039-6257(99)00029-6.
Apoptosis is a genetically controlled form of cell death that ganglion cells undergo during normal development of the retina and in diseases affecting the optic nerve, such as glaucoma. This mechanism of cell death is controlled by specific genes and their products that are activated in the dying cell. To date, the mechanism of ganglion cell apoptosis is poorly understood, but research on cell death in other areas has provided a blueprint for the study of dying ganglion cells in animal models. Extensive research of the genetic pathways of apoptosis of neurons, in general, has yielded new information about the principal genes that are involved in this process. This review is meant to survey the major genetic players that are active in neuronal cell death and discuss their possible roles in retinal ganglion cells. One of the primary regulatory steps is the activation of the tumor-suppressor protein, p53. This protein functions as a transcription factor that can up-regulate the expression of the proapoptotic gene bax and down-regulate the expression of the antiapoptotic gene brl-2. Changes in the concentrations of these gene products can further stimulate apoptotic events, including changes in mitochondria that ultimately lead to the activation of a family of cysteine proteases called caspases that digest the dying cell from within. An understanding of the genetic pathways of apoptosis may lead to the design of new treatments that could prevent its activation or arrest the process when started.
细胞凋亡是一种由基因控制的细胞死亡形式，在视网膜正常发育过程中以及在影响视神经的疾病（如青光眼）中，神经节细胞会经历这种过程。这种细胞死亡机制由在垂死细胞中被激活的特定基因及其产物控制。迄今为止，神经节细胞凋亡的机制仍知之甚少，但其他领域关于细胞死亡的研究为在动物模型中研究垂死的神经节细胞提供了一个蓝图。总体而言，对神经元凋亡遗传途径的广泛研究已经产生了关于参与这一过程的主要基因的新信息。这篇综述旨在概述在神经元细胞死亡中活跃的主要基因参与者，并讨论它们在视网膜神经节细胞中的可能作用。其中一个主要的调节步骤是肿瘤抑制蛋白p53的激活。这种蛋白质作为一种转录因子，可以上调促凋亡基因bax的表达，并下调抗凋亡基因bcl-2的表达。这些基因产物浓度的变化可以进一步刺激凋亡事件，包括线粒体的变化，最终导致一类称为半胱天冬酶的半胱氨酸蛋白酶家族的激活，这些酶从内部消化垂死细胞。对凋亡遗传途径的理解可能会导致设计出新的治疗方法，这些方法可以防止其激活或在其启动时阻止这一过程。
