Apoptosis of retinal ganglion cells in glaucoma: An update of the molecular pathways involved in cell death

Apoptosis is a genetically controlled form of cell death that ganglion cell s undergo during normal development of the retina and in diseases affecting the optic nerve, such as glaucoma. This mechanism of cell death is control led by specific genes and their products that are activated in the dying ce ll. 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 g enetic pathways of apoptosis of neurons, in general, has yielded new inform ation about the principal genes that are involved in this process. This rev iew is meant to sun:ey the major genetic players that are active in neurona l cell death and discuss their possible roles in retinal ganglion cells. On e 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 bcl-2. Changes in the concentrations of these gene products can further stimulate apoptotic events, including ch anges 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 desi gn of new treatments that could prevent its activation or arrest the proces s when started. (C) 1999 by Elsevier Science Inc. All rights reserved.